• As specialty products, therapies for ulcerative colitis (UC) can be expensive, and formulary positioning is paramount to product uptake. Payers are settled in vital contracts that lead them to prioritize broad immunology drugs Humira and Remicade. This has posed a high barrier for newer entrants to the market, which cannot compete in volume and rebates. Biosimilar and generic competition will further undermine the likely premium pricing of newer and pipeline products.
  作为专科药品，溃疡性结肠炎(UC)治疗药物价格昂贵，医保目录准入对产品市场渗透至关重要。支付方已签订关键合约，优先考虑广泛使用的免疫类药物修美乐(Humira)和类克(Remicade)。这对市场新进入者构成极高壁垒，因其无法在销量和返利方面竞争。生物类似药和仿制药的竞争将进一步削弱新上市及研发管线产品的高溢价空间。

• Following the launch of Amjevita in the US market in early 2023, a slew of adalimumab biosimilars launched midway through 2023. While biosimilar ustekinumab has entered the US market in 2025, generic tofacitinib is expected to launch in 2026. Notably, generics have fewer barriers to entry than biosimilars due to factors including their less complex nature and longstanding familiarity, facilitating a much faster and stronger erosion of branded sales.
  随着 2023 年初 Amjevita 在美国市场上市，2023 年中期一批阿达木单抗生物类似药相继推出。虽然乌司奴单抗生物类似药已于 2025 年进入美国市场，但托法替尼仿制药预计将于 2026 年上市。值得注意的是，由于结构相对简单且临床认知度高等因素，仿制药的准入壁垒低于生物类似药，能更快更大幅度地侵蚀原研药市场份额。

• Stelara biosimilars first hit the US market in January 2025, following licensing deals and patent expiry in 2024 and eight biosimilars have launched in the US since. Following the launch of biosimilars in the US, Stelara sales slumped to $981mil in the US in Q1 2025, a 42% drop compared to Q4 2024 which saw Stelara generate $1699mil.
  2025 年 1 月，随着许可协议达成和 2024 年专利到期，Stelara 生物类似药首次登陆美国市场，迄今已有八款生物类似药在美上市。生物类似药上市后，Stelara 在 2025 年第一季度美国销售额骤降至 9.81 亿美元，较 2024 年第四季度的 16.99 亿美元暴跌 42%。

• Datamonitor Healthcare estimates that in 2024, there were 2.1 million diagnosed prevalent cases of UC in the US, Japan, and five major European markets. By 2043, Datamonitor Healthcare forecasts that the number of diagnosed prevalent cases of UC will increase to 2.3 million.
  Datamonitor Healthcare 数据显示，2024 年美国、日本及欧洲五大主要市场的溃疡性结肠炎确诊患病病例达 210 万例。该机构预测，到 2043 年这一数字将增长至 230 万例。

• Pfizer’s Velsipity was approved in October 2023 and is the latest oral agent in the UC market. The drug is a novel prospect for the market as an S1P1, S1P4, and S1P5 receptor modulator, and will challenge Zeposia, a fellow S1P receptor modulator.
  辉瑞公司的 Velsipity 于 2023 年 10 月获批，成为溃疡性结肠炎市场最新口服制剂。作为 S1P1、S1P4 和 S1P5 受体调节剂，该药物为市场带来全新治疗选择，将与同属 S1P 受体调节剂的 Zeposia 形成竞争。

• Johnson & Johnson’s Simponi’s patent expired in 2024 and biosimilars from Alvotech and Bio-Thera Solutions have filed for regulatory approval in the US.
  强生公司的 Simponi 专利于 2024 年到期，目前 Alvotech 和百奥泰生物制药的生物类似药已向美国监管部门提交上市申请。

• AbbVie’s Skyrizi and Johnson & Johnson’s Tremfya are the latest to join the UC market with former gaining FDA approval in June 2024 and the latter with an FDA approval in September 2024.
  艾伯维的 Skyrizi 和强生的 Tremfya 是最新加入溃疡性结肠炎市场的药物，前者于 2024 年 6 月获得食品药品监督管理局批准，后者则在 2024 年 9 月获批。

• Although the anti-TNF class is the cornerstone of treatment, ~10–30% of patients are non-responders to initial treatment, and ~23–46% of patients lose response over time. Additionally, the class has black box warnings for the risk of serious infections and malignancy. These drugs are favored due to longstanding physician familiarity and prioritization in formularies; however, they do not satisfy persisting unmet needs in the UC market.
  虽然抗 TNF 类药物是治疗的基石，但约 10-30%的患者对初始治疗无反应，约 23-46%的患者会随时间推移失去疗效。此外，这类药物还附有关于严重感染和恶性肿瘤风险的黑框警告。由于内科医生长期以来的熟悉程度和处方集优先考虑，这些药物仍受青睐；但它们未能满足溃疡性结肠炎市场持续存在的未满足需求。

• Critical unmet needs and opportunities include demonstrating strong efficacy to treat inadequate responders, clinically balanced drugs that offer both efficacy and safety, producing superior data over anti-TNF inhibitors and available drugs in the same class through head-to-head trials, and competitive pricing, which is essential to facilitate better positioning in the treatment algorithm.
  关键的未满足需求和机遇包括：证明对治疗反应不足患者具有显著疗效，提供疗效与安全性临床平衡的药物，通过头对头试验产生优于抗 TNF 抑制剂和同类现有药物的数据，以及具有竞争力的定价策略——这对在治疗算法中获得更有利地位至关重要。

• Promising novel mechanisms of action being pursued in UC include drugs binding to cytoplasmic cap-binding complex (obefazimod) and drugs targeting the TL1A receptor (RVT-3101 and MK-7240).
  治疗溃疡性结肠炎(UC)具有前景的新作用机制药物包括：靶向细胞质帽结合复合体的药物(奥贝法莫德)以及靶向 TL1A 受体的药物(RVT-3101 和 MK-7240)。

Ulcerative colitis (UC) is a form of chronic inflammatory bowel disease (IBD) that causes mucosal inflammation affecting the colon. The idiopathic inflammation is commonly associated with the rectum (proctitis) and may extend proximally, evolving into left-sided colitis or extensive colitis (see the figure below). UC typically presents with bloody diarrhea, which may manifest alongside mucus, rectal urgency, tenesmus, and abdominal pain. The disease course is relapsing and remitting with intermittent periods of acute exacerbation, which may be serious enough to warrant therapy escalation, hospitalization, or even colectomy.
溃疡性结肠炎(UC)是一种慢性炎症性肠病(IBD)，会导致结肠黏膜炎症。这种特发性炎症通常累及直肠(直肠炎)，并可能向近端延伸，发展为左侧结肠炎或广泛性结肠炎(见下图)。UC 典型症状为血性腹泻，可能伴随黏液便、里急后重、便意频繁及腹痛。该疾病呈反复发作和缓解的病程，急性加重期可能严重到需要升级治疗、住院甚至进行结肠切除术。

UC has a significant impact on patients’ morbidity, and less so on mortality. The prevalence of concomitant Clostridium difficile (C. diff) infection in newly diagnosed or relapsing IBD is in the range of 5–47%, and is associated with poor prognosis and higher mortality rates. Patients with active UC are at greater risk of co-morbid anxiety, depression, and impaired social interactions. In the long term, there is an elevated risk of dysplasia and colorectal cancer.
溃疡性结肠炎对患者的发病率有显著影响，但对死亡率影响较小。在新确诊或复发的炎症性肠病患者中，艰难梭菌合并感染率为 5-47%，这种情况与预后不良和更高死亡率相关。活动期溃疡性结肠炎患者更容易出现焦虑、抑郁等共病及社交障碍。长期来看，患者发生异型增生和结直肠癌的风险也会升高。

Patient segmentation  患者分型

There is no standard definition of disease severity in the treatment guidelines available for UC. Patients’ disease severity may range from remission to mild, moderate, or severe UC. A small proportion of patients experience fulminant disease (rapid-onset, progressive colitis).
现有溃疡性结肠炎治疗指南中尚未对疾病严重程度作出统一定义。患者病情可能处于缓解期，或表现为轻度、中度及重度溃疡性结肠炎。少数患者会经历暴发性结肠炎（快速发作的进行性结肠炎）。

The historical treatment of UC was based on mesalamine 5-aminosalicylic acid (5-ASA) compounds, corticosteroids, and thiopurines, until the emergence of anti-tumor necrosis factor (TNF) inhibitors in the late 1990s. Anti-TNFs were seen as a major clinical advance in the IBD disease segment but approximately one-third of the patients are non-responders. Drugs with alternative mechanisms of action, some with more convenient formulations and routes of administration have since been launched offering patients and physicians with options in the treatment of UC. More recently, the therapeutic armamentarium for UC has expanded to include the Janus kinase (JAK) inhibitor, human IL-12 and IL-23 antagonists and S1P receptor modulators. Emergency surgery may be appropriate for refractory toxic megacolon, colonic perforation, or severe colorectal bleeding.
溃疡性结肠炎的传统治疗主要基于美沙拉嗪 5-氨基水杨酸(5-ASA)化合物、皮质类固醇和硫嘌呤类药物，直至 20 世纪 90 年代末抗肿瘤坏死因子(TNF)抑制剂问世。抗 TNF 药物被视为炎症性肠病治疗领域的重大临床突破，但约三分之一患者无应答。此后，具有不同作用机制的药物陆续上市，其中部分采用更便捷的剂型和给药途径，为患者和医生提供了更多治疗选择。近年来，溃疡性结肠炎的治疗方案进一步扩展至包含 Janus 激酶(JAK)抑制剂、人源 IL-12 与 IL-23 拮抗剂以及 S1P 受体调节剂。对于难治性中毒性巨结肠、结肠穿孔或严重结直肠出血病例，紧急手术可能是适宜选择。

The treatment strategy for UC is dependent on a number of considerations, such as disease severity, distribution, and prognosis. The goal of treatment is achieving and maintaining steroid-free remission through induction and maintenance therapy. An emerging treatment goal is mucosal healing, which is pertinent to long-term outcomes. The American College of Gastroenterology (ACG), American Gastroenterology Association (AGA), the European Crohn’s and Colitis Organization (ECCO), and the National Institute for Health and Care Excellence (NICE) have produced treatment guidelines for the management of UC.
溃疡性结肠炎的治疗策略取决于多种因素，如疾病严重程度、病变范围和预后。治疗目标是通过诱导和维持治疗实现并保持无类固醇缓解。黏膜愈合作为新兴治疗目标，与长期预后密切相关。美国胃肠病学会（ACG）、美国胃肠病协会（AGA）、欧洲克罗恩病和结肠炎组织（ECCO）以及英国国家健康与护理卓越研究所（NICE）均已制定溃疡性结肠炎的治疗指南。

ACG treatment guidelines  美国胃肠病学会治疗指南

The 2019 ACG guidelines provide recommendations for the treatment of mild UC, moderate-to-severe UC, and hospitalized patients with acute severe UC.
2019 年 ACG 指南针对轻度 UC、中重度 UC 以及急性重度 UC 住院患者的治疗提供了建议。

AGA treatment guidelines  AGA 治疗指南

The 2024 AGA guidelines provide recommendations for the treatment of moderate to severe UC.
2024 年 AGA 指南为中重度 UC 的治疗提供了建议。

ECCO treatment guidelines
ECCO 治疗指南

The 2021 ECCO guidelines provide recommendations according to disease severity (mildly to moderately active disease and moderately to severely active disease).
2021 年 ECCO 指南根据疾病严重程度（轻度至中度活动性疾病和中度至重度活动性疾病）提供了治疗建议。

NICE treatment guidelines
NICE 治疗指南

The 2019 NICE guidelines provide recommendations for inducing and maintaining remission for all disease extents and severities.
2019 年 NICE 指南针对所有疾病范围和严重程度提供了诱导及维持缓解的治疗建议。

Last Reviewed:  最后审阅日期：
05 Sep, 2024  2024 年 9 月 5 日

by Asma Ali  作者：Asma Ali

Overview  概述

Methodology  方法论

We undertook market-specific literature reviews in order to provide a robust analysis of the diagnosed prevalent UC population in the US, Japan, and five major European markets. A variety of secondary data sources were identified, including literature reviews and epidemiological study reports, before quality appraisal, forming a robust foundation on which to model and forecast the patient population. Sources were evaluated for inclusion based on their epidemiological quality, including study settings, demographic sample profiles, sampling procedures and sample size, and potential sources of bias. Prevalence proportions were extracted, by age and gender where available, for diagnosed UC.
为全面分析美国、日本及欧洲五大主要市场的溃疡性结肠炎确诊患病率，我们开展了针对性文献综述。通过筛选文献综述与流行病学研究报告等二手数据源，经质量评估后构建了可靠的病患群体建模与预测基础。数据源的纳入标准包括流行病学质量（研究环境、人口样本特征、抽样流程与样本量、潜在偏差来源等）。在数据可得情况下，我们按年龄和性别维度提取了确诊溃疡性结肠炎的患病率数据。

This analysis covers individuals of all ages, as UC can be diagnosed and prevalent at any age (Cosnes et al., 2011).
本分析涵盖所有年龄段人群，因溃疡性结肠炎可在任何年龄被诊断和发病（Cosnes 等人，2011 年）。

Disease definition  疾病定义

There is no universal standard approach to UC diagnosis. Instead, diagnosis is based on a combination of endoscopic, histological, radiological, and/or biochemical investigations. For the purpose of this forecast, diagnosed UC cases were defined as follows:
目前尚无统一的溃疡性结肠炎诊断标准。诊断需结合内窥镜检查、组织学检查、影像学检查和/或生化检测结果综合判断。在本预测模型中，确诊的溃疡性结肠炎病例定义如下：

• International Classification of Diseases (ICD)-10 code K51.x.
  国际疾病分类（ICD）-10 代码 K51.x

• ICD-9 code 556.x.  国际疾病分类（ICD）-9 代码 556.x

• Cases identified using the diagnostic approach recommended by the second European evidence-based consensus on the diagnosis and management of ulcerative colitis, and consistent with recommendations of the American College of Gastroenterology (Kornbluth and Sachar, 2010). Diagnosis is established by a combination of medical history, clinical evaluation, and typical endoscopic and histological findings, with infective cause excluded through a stool sample (Dignass et al., 2012).
  采用欧洲第二版循证共识关于溃疡性结肠炎诊断与管理的推荐方法，并符合美国胃肠病学会诊疗指南（Kornbluth 和 Sachar，2010 年）的病例。诊断需结合病史采集、临床评估、典型内镜及组织学表现综合判定，并通过粪便样本排除感染性病因（Dignass 等，2012 年）。

• For populations using a health insurance provider as the sampling frame, individuals with at least one claim for UC who also had at least one pharmacy claim for an IBD-specific medication (University of Minnesota IBD Epidemiology Database definition; validated by Bernstein et al. [1999]).
  以健康保险提供方作为抽样框架的人群中，至少有一次溃疡性结肠炎（UC）理赔记录且至少有一次炎症性肠病（IBD）专用药物药房理赔记录的个人（采用明尼苏达大学 IBD 流行病学数据库定义；经 Bernstein 等人[1999 年]验证）。

• For studies where the specific diagnosis method was not described, primary or secondary care data describing a specific UC diagnosis were accepted.
  对于未描述具体诊断方法的研究，接受描述明确 UC 诊断的初级或二级医疗数据。

Details of sources and methodologies used are provided in the table below.
所用数据源和方法学细节详见下表。

Data sources  数据来源

The table below details the sources used to estimate UC prevalence in the US, Japan, and five major European markets.
下表详述了用于估算美国、日本及欧洲五大主要市场溃疡性结肠炎患病率的数据来源。

Country-specific methods  国别研究方法

US and Japan  美国和日本

Age- and gender-specific prevalence rates for individuals aged 0–65 years were extracted from a study by Yamazaki et al. (2023). The study utilized two large separate medical insurance claims databases to determine the diagnosed prevalence of UC in the US and Japan. Cases were determined using ICD-9 and ICD-10 codes.
年龄和性别特异性患病率数据（针对 0-65 岁人群）引自 Yamazaki 等人(2023)的研究。该研究利用两个独立的大型医疗保险理赔数据库，确定了美国和日本溃疡性结肠炎(UC)的确诊患病率。病例判定采用 ICD-9 和 ICD-10 编码标准。

For the US, the IBM MarketScan Commercial Claims and Encounters (CCAE) database was used. It includes health insurance claims for providers that cover more than 155 million lives (~46% of the total US population). Claims come from inpatient, outpatient, outpatient pharmacy, behavioral healthcare, and enrollment data of employees of large corporations and health plans across the US.
美国数据来源于 IBM MarketScan 商业理赔及就诊(CCAE)数据库。该数据库涵盖承保超过 1.55 亿人（约占美国总人口 46%）的医疗服务提供商理赔数据，包含来自全美大型企业雇员及健康计划的住院、门诊、门诊药房、行为医疗以及参保数据。

For Japan, the Japan Medical Data Center (JMDC) is a payer-based database collecting claims data covering non-government employees of large corporations aged 18–65 years and their dependents (children <18 years of age and adults aged <75 years). The dataset included approximately 14 million lives in Japan (~ 10% of the total Japanese population). Claims data are derived from monthly claims issued by clinics, hospitals, and pharmacies. The JMDC database captures all inpatient, outpatient, and pharmaceutical services provided to its members, including diagnoses, surgical procedures, and medications.
在日本，日本医疗数据中心（JMDC）是一个基于支付方的数据库，收集了 18 至 65 岁大型企业非政府雇员及其家属（18 岁以下儿童和 75 岁以下成人）的理赔数据。该数据集覆盖了日本约 1400 万人口（约占日本总人口的 10%）。理赔数据来源于诊所、医院和药房每月提交的理赔记录。JMDC 数据库囊括了为其会员提供的所有住院、门诊和药品服务信息，包括诊断、手术操作和用药记录。

France  法国

Due to the paucity of data available for the diagnosed prevalence of UC in France, age- and gender-specific prevalence rates for Germany were used and applied to French population numbers to determine diagnosed prevalent cases of UC in France (see below for Germany).
由于法国溃疡性结肠炎确诊患病率数据匮乏，研究采用了德国分年龄和性别的患病率数据，并将其应用于法国人口数量来推算法国的溃疡性结肠炎确诊患病病例数（德国数据详见下文）。

Germany  德国

A study by Hein et al. (2014) was used to determine diagnosed prevalence rates of UC in Germany. Age- and gender-specific prevalence rates were extracted from this study, which used data from a claims database from a large German statutory health insurance (SHI) fund (AOK) located in the federal state of Hesse and covering approximately 37% of all members of the SHI system in Germany. A random sample of 18.75% of AOK members was analyzed. Cases were defined based on ICD-10-GM (German Modification) code K51 through inspection of hospital inpatient and discharge notes or diagnosis code at death.
Hein 等人(2014 年)的研究被用于确定德国溃疡性结肠炎(UC)的诊断患病率。该研究从德国黑森州大型法定医疗保险基金(AOK)的理赔数据库中提取数据，覆盖了德国约 37%的法定医保参保人员，并据此得出各年龄层和性别的患病率。研究分析了 AOK 参保人员 18.75%的随机样本，病例定义基于 ICD-10-GM(德国修订版)编码 K51，通过检查住院病历、出院记录或死亡诊断编码进行确认。

Italy  意大利

A population-based study by Crocetti et al. (2021) was used to determine the diagnosed prevalence of UC in Italy. The study used data from the Milan Agency for Health Protection to determine the prevalence of UC in the northern region of Lombardy and estimated prevalence of UC in Italy. Age- and gender-specific diagnosed prevalence rates were extracted. IBD cases were identified among the residents in the area (about 3.5 million) registered with the regional universal coverage healthcare system using ICD-9-CM and internal hospital codes.
Crocetti 等人(2021 年)基于人群的研究被用于确定意大利溃疡性结肠炎的诊断患病率。该研究利用米兰健康保护机构的数据，确定了伦巴第大区的 UC 患病率，并推算了意大利全国的患病情况。研究提取了分年龄和性别的诊断患病率数据。通过 ICD-9-CM 编码和医院内部编码，在约 350 万注册于区域全民医保系统的居民中识别出炎症性肠病(IBD)病例。

Spain  西班牙

Gender-specific prevalence proportions were extracted from a retrospective, multicenter study by Lucendo et al. (2014) carried out within the Ciudad Real province IBD working group, which represents all of the adult IBD units in the region. The recruitment area for this study included five public hospitals located in the Ciudad Real province in central Spain. Age-specific ratios were calculated from the Italian study by Crocetti et al. and applied to the gender-specific proportions to determine the age- and gender-specific diagnosed prevalence proportions of UC for Spain.
性别特异性患病率数据取自 Lucendo 等人(2014)在雷阿尔城省 IBD 工作组内开展的一项回顾性多中心研究，该工作组代表了该地区所有成人 IBD 诊疗单位。该研究的招募范围覆盖西班牙中部雷阿尔城省的五所公立医院。年龄特异性比率则采用 Crocetti 等人在意大利研究中计算的数据，结合性别特异性比例推算出西班牙溃疡性结肠炎在年龄与性别维度的确诊患病率分布。

UK  英国

Gender-specific prevalent rates for adults aged 18 years and over were extracted from a cross-sectional study conducted by King et al. (2020) to calculate the diagnosed prevalence of UC in the UK. Data were extracted from The Health Improvement Network (THIN) primary care database derived from 787 general practices across the UK. Cases were defined based on diagnosis with a clinical (Read) code. Clinical code lists used to identify patients with UC were previously validated. Age distribution ratios from a Scottish study by Jones et al. (2019) were applied to gender-specific prevalence proportions (18+ years); prevalence in children aged under 18 years was estimated using ratios calculated Jones et al.
18 岁及以上成年人的性别特异性患病率数据取自 King 等人（2020 年）开展的横断面研究，用于计算英国溃疡性结肠炎（UC）的诊断患病率。研究数据来源于覆盖英国 787 家全科诊所的初级医疗数据库"健康改善网络"（THIN）。病例根据临床诊断（Read）编码进行界定，所用溃疡性结肠炎临床编码清单已通过前期验证。研究采用 Jones 等人（2019 年）苏格兰地区研究的年龄分布比率对 18 岁以上人群的性别患病比例进行校正，18 岁以下儿童患病率则使用 Jones 团队计算的比率进行估算。

Forecasting  预测方法

To calculate the number of diagnosed prevalent cases of UC in the 2023–43 forecast period, we multiplied calculated prevalence proportions by the corresponding country-, age-, and gender-specific population estimates from the UN World Population Prospects database (United Nations, 2022). The UN database was chosen as a reliable population denominator; the data include standard sets of demographic indicators and populations by five-year age group and gender. The forecasted numbers of prevalent cases were validated against national benchmarks where possible, in order to check for any inconsistencies or unusual trends in the analysis.
为计算 2023-2043 年预测期内溃疡性结肠炎(UC)的确诊患病病例数，我们将计算的患病率比例乘以联合国《世界人口展望》数据库(United Nations, 2022)中相应国家、年龄和性别人口数据。选择联合国数据库作为可靠的人口基数参考，该数据包含按五岁年龄组和性别划分的标准人口统计指标。预测患病病例数尽可能与国家基准数据进行验证，以检查分析中是否存在不一致或异常趋势。

We dynamically modeled age- and gender-specific prevalence rates instead of using a static model, employing an in-house VBA model. This allows for a more accurate representation of the changing prevalence rates in different age groups.
我们采用自主研发的 VBA 模型对特定年龄和性别的患病率进行动态建模，而非使用静态模型。这种方法能更准确地反映不同年龄组患病率的变化趋势。

Last Reviewed:  最后审阅日期：
10 Sep, 2024  2024 年 9 月 10 日

by Joseph Jacob and Sonny Nghiem
作者：约瑟夫·雅各布与桑尼·阮

Overview  概述

The UC market will expand significantly over the 2024–33 forecast period, with sales in the US, Japan, and five major European markets increasing overall from $6.9bn to $11.1bn at a compound annual growth rate (CAGR) of 5.4%. UC sales are expected to peak in 2031 at $11.4bn before eroding in 2032 onwards owing to patent expiries for several drugs and opportunistic biosimilar competition. Although overall UC sales are set to increase in all forecasted geographies over 2024–33, the fast-expanding US segment will be the major growth driver.
在 2024 至 2033 年预测期内，溃疡性结肠炎（UC）市场将显著扩张，美国、日本及欧洲五大主要市场的销售额预计将从 69 亿美元增至 111 亿美元，复合年增长率（CAGR）达 5.4%。受多款药物专利到期及生物类似药 opportunistic 竞争影响，UC 销售额将在 2031 年达到 114 亿美元的峰值后，于 2032 年起逐步下滑。尽管所有预测地区的 UC 销售额在 2024-2033 年间均呈增长态势，快速扩张的美国市场将成为主要增长驱动力。

Key themes  关键主题

[1] Despite all currently available key marketed brands facing generic/biosimilar competition in the US, Japan, and five major European markets during the forecast period, UC market expansion will be propelled by several launches of pipeline products and ever-increasing interest in oral formulations.
[1] 尽管当前所有已上市关键品牌药物在预测期内都将面临美国、日本及欧洲五大市场的仿制药/生物类似药竞争，但管线产品的陆续上市及口服制剂日益增长的关注度将持续推动 UC 市场扩张。

[2] Potential launches planned in the coming years will promote intra-class competition. New launches will challenge existing brands such as Stelara, which will face competition from Omvoh and Tremfya, and Zeposia, which will face competition from Velsipity.
[2] 未来数年计划推出的新药将加剧同类药物竞争。Omvoh 与 Tremfya 将对 Stelara 形成挑战，Velsipity 则将与 Zeposia 展开竞争。

[3] Biosimilars will play a large part in the UC space over the forecast period, with notable sales predicted for biosimilar versions of adalimumab, ustekinumab, and infliximab. Biosimilar versions of Humira have already entered the US market, with biosimilars to Stelara expected in late 2024/early 2025, and substantial market deterioration is expected for the branded versions.
[3] 在预测期内，生物类似药将在溃疡性结肠炎领域发挥重要作用，阿达木单抗、乌司奴单抗和英夫利昔单抗的生物类似药预计将取得显著销售额。修美乐的生物类似药已进入美国市场，而斯特拉拉的生物类似药预计将于 2024 年底/2025 年初上市，原研药的市场份额预计将大幅萎缩。

[4] Novel mechanisms of action including RVT-3101 and MK-7240 targeting the TL1A receptor, as well as cytoplasmic cap-binding complex agonist obefazimod, are targeting unmet needs and are forecast to compete with established therapies.
[4] 包括靶向 TL1A 受体的 RVT-3101 和 MK-7240，以及细胞质帽结合复合物激动剂 obefazimod 在内的新型作用机制药物，正瞄准未满足的临床需求，预计将与现有疗法形成竞争。

Methodology  方法论

We use a patient-based approach to size the commercial potential of the UC market across the US, Japan, and five major European markets. This analysis contains an assessment of key UC therapies on the market and in the late-phase pipeline, a discussion of UC market dynamics, and a 10-year patient-based sales forecast.
我们采用基于患者数量的方法，评估了美国、日本和欧洲五大主要市场的溃疡性结肠炎商业潜力。该分析包含对已上市及后期研发阶段关键疗法的评估、溃疡性结肠炎市场动态的讨论，以及基于患者数量的十年销售预测。

Q3 2024 model updates  2024 年第三季度模型更新

• Forecast period extended to 2033
  预测期延长至 2033 年

• Epidemiology data updated
  流行病学数据已更新

• US, 5EU, and Japan epidemiology updated
  美国、五大欧盟国家及日本流行病学数据已更新

• Skyrizi added to the forecast
  已将 Skyrizi 纳入预测

• MK-7240 added to the forecast
  已将 MK-7240 纳入预测

• RVT-3101 added to the forecast
  RVT-3101 加入预测清单

• Entyvio SC added to the forecast
  Entyvio SC 加入预测清单

• Obefazimod added to the forecast
  Obefazimod 加入预测清单

• Omvoh moved to marketed drugs
  Omvoh 转入已上市药品目录

• Velsipity moved to marketed drugs
  维乐西匹（Velsipity）转入上市药品目录

• Skyrizi patent expiry dates added
  新增 Skyrizi 专利到期日期

• Entyvio loss of exclusivity date updated
  更新恩泰优（Entyvio）独占权丧失日期

• Humira sales adjusted lower
  修美乐（Humira）销售额下调

• Rinvoq sales adjusted slightly higher
  瑞福乐（Rinvoq）销售额微幅上调

• Stelara sales adjusted lower       
  喜达诺（Stelara）销售额下调

• Xeljanz sales adjusted lower
  尚杰（Xeljanz）销售额下调

• Zeposia sales adjusted lower
  泽布西亚销售额下调

• Biosimilar adalimumab market shares adjusted lower
  阿达木单抗生物类似药市场份额下调

• Kappaproct removed from the forecast.
  卡帕普洛特已从预测中移除。

Q1 2023 model updates  2023 年第一季度模型更新

• Forecast extended to 2032
  预测期延长至 2032 年

• Tremfya added to the forecast
  特雷姆菲亚已加入预测

• Jyseleca approved in EU and Japan

• Biosimilar adalimumab moved to marketed drugs

• Biosimilar vedolizumab launch updated to 2032

• Entyvio patent expiry dates updated in EU and Japan

• Zeposia loss of exclusivity dates added in US and EU

• Entyvio sales adjusted higher

• Humira sales adjusted slightly higher

• Rinvoq sales adjusted slightly lower

• Simponi sales adjusted slightly higher

• Stelara sales adjusted slightly higher

• Xeljanz sales adjusted lower

• Zeposia sales adjusted slightly lower

• Biosimilar adalimumab sales adjusted slightly lower

• Biosimilar infliximab sales adjusted slightly lower

• Etrasimod sales adjusted higher

• Kappaproct sales adjusted slightly higher

• Mirikizumab sales adjusted lower

• Biosimilar ustekinumab sales adjusted lower

• Generic tofacitinib sales adjusted lower.

Q3 2021 post-earnings model updates (1 December 2021)

• Product sales updated with company-reported figures

• Stelara forecast adjusted lower

• Xeljanz forecast adjusted slightly lower

• Rinvoq forecast adjusted slightly higher.

Q4 2020 post-earnings model updates (1 April 2021)

• Forecast extended to 2030

• Product sales updated with company-reported figures

• 2021 pricing updated

• Simponi forecast adjusted slightly higher

• Xeljanz forecast adjusted slightly higher

• Etrasimod forecast adjusted higher

• Jyseleca forecast adjusted slightly higher

• Kappaproct forecast adjusted higher

• Biosimilar adalimumab forecast adjusted higher

• Biosimilar infliximab forecast adjusted higher

• Generic tofacitinib forecast adjusted slightly higher

• Biosimilar vedolizumab forecast adjusted slightly lower.

Clinical performance is important in driving a product’s success in UC; however, the overriding differentiator between products is market access. Therefore, market access carries the most weight within the commercial attributes of our drug assessment model, alongside generic competition risk. As specialty products, therapies for UC can be expensive, and formulary positioning is paramount to product uptake. Payers are settled in vital contracts that lead them to prioritize broad immunology drugs Humira and Remicade. This has posed a high barrier for newer entrants to the market, which cannot compete in volume and rebates. Biosimilar and generic competition will further undermine the likely premium pricing of newer drugs and pipeline products.
临床表现在推动溃疡性结肠炎治疗产品成功方面固然重要，但产品间最关键的差异化因素仍是市场准入。因此，在我们药品评估模型的商业属性中，市场准入权重最高，仅次于仿制药竞争风险。作为专科药物，UC 治疗药物价格昂贵，医保目录准入对产品市场渗透至关重要。支付方已与重要合约绑定，这使他们优先考虑广谱免疫药物修美乐和类克。这为市场新进入者设置了极高门槛，使其难以在销量和返利方面竞争。生物类似药与仿制药的竞争将进一步削弱新药及在研产品获得溢价定价的可能性。

Biologic disease-modifying antirheumatic drugs (DMARDs)
生物类疾病修饰抗风湿药物（DMARDs）

Anti-TNF inhibitors  抗肿瘤坏死因子抑制剂

• Although the anti-TNF class possesses a stronghold at the first line of biologic therapy in the UC treatment algorithm, ~30% of patients are non-responders to initial treatment, and ~23–46% of patients lose response over time. Furthermore, the class has black box warnings for the risk of serious infections and malignancy. These drugs are favored due to longstanding physician familiarity and prioritization in formularies; however, they do not satisfy persisting unmet needs in the UC market. Thus, they are scored poorly for clinical attractiveness in our drug assessment model.
  尽管抗 TNF 类药物在溃疡性结肠炎治疗算法的一线生物疗法中占据主导地位，但约 30%的患者对初始治疗无应答，约 23-46%的患者会随时间推移丧失疗效。此外，该类药物还附有关于严重感染和恶性肿瘤风险的黑框警告。由于内科医生长期使用习惯及医保目录的优先覆盖，这类药物仍受青睐；然而它们未能满足溃疡性结肠炎市场持续存在的未竟需求。因此，在我们的药物评估模型中，其临床吸引力评分较低。

• Of the anti-TNF inhibitors, Remicade (infliximab) has the highest clinical score since it is specifically approved for maintaining mucosal healing and eliminating corticosteroid use. A meta-analysis by Singh et al. (2020) found that Remicade was the highest-ranking drug for induction of clinical remission and endoscopic improvement in biologic-naïve patients. Biosimilar uptake, especially of Pfizer’s Inflectra, has risen, as they are replacing Remicade to find favorable formulary positioning. Although Remicade benefits from the extensive commercial resources and marketing experience, biosimilar competition has slowly eroded sales. This trend is likely to continue as Celltrion's subcutaneous infliximab, Zymfentra, gained approval in October 2023. Although Inflectra is an infliximab biosimilar that references Remicade, Zymfentra was approved through the stand-alone biologics license application process. It is considered a new drug due to its regulatory pathway under section 351(a). It has patent protection through 2037 for its dosage form and 2040 for its route of administration. Zymfentra has found favorable formulary positioning having signed an agreement with Express Scripts.
  在抗 TNF 抑制剂中，类克（英夫利昔单抗）凭借其专门获批用于维持黏膜愈合和停用皮质类固醇的适应症，获得了最高的临床评分。Singh 等人（2020 年）的 Meta 分析显示，在未接受过生物制剂治疗的患者中，类克是诱导临床缓解和内镜改善效果最佳的药物。随着生物类似物（尤其是辉瑞的英夫利西）逐步替代原研药以获得更有利的医保目录地位，其使用率持续上升。尽管类克受益于强大的商业资源和营销经验，但生物类似物的竞争已逐渐侵蚀其销售额。随着 Celltrion 公司的皮下注射剂型英夫利昔单抗 Zymfentra 于 2023 年 10 月获批，这一趋势或将延续。虽然英夫利西是参照类克开发的生物类似物，但 Zymfentra 通过独立生物制品许可申请程序获批。根据《公共卫生服务法》第 351(a)条款的监管路径，它被视为新药，其剂型专利保护至 2037 年，给药途径专利至 2040 年。Zymfentra 已与快捷药方公司达成协议，获得了有利的医保目录准入地位。

"In my experience I think Remicade is probably the most efficacious agent we have available.” – US key opinion leader
"根据我的经验，我认为类克可能是我们现有药物中疗效最佳的。"——美国关键意见领袖

“So, infliximab, I’d say improvement within 14 days, and usually at six weeks you have got a full response. In some patients you find that you need to adjust the dosing and they take a little bit longer, but usually at six weeks you either have the response that you’re going to get or you haven’t achieved a response and then it’s probably not worthwhile persevering much longer. So I think in terms of, if you want really speedy drugs, infliximab and tofacitinib are probably the fastest.” – EU key opinion leader
“以英夫利昔单抗为例，我认为 14 天内就能看到改善，通常 6 周内会获得完全应答。部分患者可能需要调整剂量，因此见效时间会稍长一些，但通常 6 周时要么已经获得预期疗效，要么就说明药物无效，这时可能就不值得继续坚持用药了。所以我认为，如果追求快速起效的药物，英夫利昔单抗和托法替布可能是见效最快的。”——欧盟关键意见领袖

“The first-line treatment, in terms of biologics or small molecules, for us is infliximab.” – EU key opinion leader
“对我们而言，生物制剂或小分子药物的一线治疗首选是英夫利昔单抗。”——欧盟关键意见领袖

• The commercial scores of Simponi (golimumab) and Humira (adalimumab) have dwindled, as the latter has already begun facing biosimilar competition. Johnson & Johnson’s Simponi’s patent expired in 2024 with biosimilars from Alvotech and Bio-Thera Solutions having completed Phase III trials. Johnson & Johnson has submitted a sBLA to the FDA seeking expanded approval of Simponi for the treatment of children two years and older with moderately to severely active UC and approval is expected in the second half of 2025. Johnson & Johnson has also completed recruitment of the Phase IIb DUET-UC trial which is investigating a combination of golimumab and guselkumab in UC. Currently, Remicade is the only approved drug for paediatric patients in UC.
  欣普尼（戈利木单抗）和修美乐（阿达木单抗）的商业评分持续走低，后者已开始面临生物类似药竞争。强生公司欣普尼的专利于 2024 年到期，目前 Alvotech 和百奥泰的生物类似药已完成 III 期临床试验。强生已向美国食品药品监督管理局提交补充生物制品许可申请，寻求扩大欣普尼适应症至治疗 2 岁及以上中重度活动性溃疡性结肠炎儿童患者，预计 2025 年下半年获批。强生还完成了 IIb 期 DUET-UC 试验的患者招募，该试验正在研究戈利木单抗与古塞库尤单抗联合治疗溃疡性结肠炎的疗效。目前，类克是唯一获批用于儿童溃疡性结肠炎患者的药物。

• Among Simponi biosimilars, Alvotech’s AVT05 and Bio-Thera’s BAT2506 are the front runners, with both biosimilars finding acceptance of European Medicines Agency (EMA) marketing authorization in November 2024 and February 2025, respectively. Bio-Thera is a step ahead in the US, with the FDA having accepted BAT2206 for review in July 2024 while Alvotech filed AVT05 earlier in 2025. Both companies have formed strategic alliances in the European and US markets to commercialize their products. Alvotech partnered with Advanz to commercialize five biosimilars in the EU, including biosimilars to Entyvio and Simponi, while the company partnered with Teva in the US to commercialize AVT05. Chinese manufacturer Bio-Thera has also formed strategic partnerships with Stada in the EU and Accord in the US to commercialize BAT2506.
  在 Simponi 生物类似药中，Alvotech 的 AVT05 和百奥泰的 BAT2506 处于领先地位，这两款生物类似药分别于 2024 年 11 月和 2025 年 2 月获得欧洲药品管理局（EMA）的上市许可。百奥泰在美国市场更胜一筹，其 BAT2206 已于 2024 年 7 月获得美国食品药品监督管理局受理审评，而 Alvotech 的 AVT05 则在 2025 年初提交申请。两家公司均在欧美市场建立了战略联盟以实现产品商业化：Alvotech 与 Advanz 合作在欧盟商业化五款生物类似药（包括 Entyvio 和 Simponi 的类似药），在美国则与 Teva 合作推广 AVT05；中国药企百奥泰也分别与欧盟的 Stada、美国的 Accord 达成战略合作，共同推进 BAT2506 的商业化进程。

“In terms of other TNFs, there are adalimumab and golimumab, and in our experience in my center, we find that those are not quite as effective as infliximab. So we use those in patients who insist on a subcutaneous administration – now that will change in the next few months because intravenous infliximab can be replaced by subcutaneous infliximab – or those who developed a reaction or antibodies to infliximab.” – EU key opinion leader
在其他 TNF 抑制剂方面，有阿达木单抗和戈利木单抗。根据我们中心的临床经验，这些药物的疗效不如英夫利昔单抗。因此，我们仅对坚持要求皮下给药的患者使用这些药物——这种情况在未来几个月会有所改变，因为静脉注射英夫利昔单抗将被皮下剂型替代——或者用于对英夫利昔单抗产生反应或抗体的患者。”——欧盟关键意见领袖

“If they failed [first-line anti-TNF] because they initially responded and then they reject the drug with anti-drug antibodies, we try and switch in-class to either adalimumab or golimumab.” – EU key opinion leader
“如果患者对[一线抗 TNF 药物]治疗失败，即最初有反应但随后因产生抗药抗体而失效，我们会尝试在同类药物中换用阿达木单抗或戈利木单抗。”——欧洲关键意见领袖

Biosimilars to Humira  修美乐生物类似药

• Since January 2023, when biosimilars to Humira began to enter the US market, these products have continued to vie for market share across immune and inflammatory disease areas. Biosimilar adalimumab entry represents a key inflection point in the US market, so we have included an overview of this landscape; however, individual biosimilars have been excluded from the drug assessment model.  
  自 2023 年 1 月修美乐生物类似药开始进入美国市场以来，这些产品持续在免疫和炎症疾病领域争夺市场份额。阿达木单抗生物类似药的上市标志着美国市场的关键转折点，因此我们对此格局进行了概述；不过具体生物类似药品种并未纳入药物评估模型。

• The market dynamics of adalimumab biosimilar have changed rapidly since the entry of adalimumab biosimilars. The key differentiator among these biosimilars is pharmacy benefit managers (PBMs) formulary inclusion. Speed to market, concentration, interchangeability status, pricing strategies, seem to play a minor role. In April 2024, CVS Caremark, one of the largest US PBMs, became the first PBM to remove Humira from its national preferred formulary, replacing it with biosimilar adalimumab versions. Following this trend, in 2025, OptumRx became the only major PBM to include Humira, but it dropped the drug to Tier 3, requiring additional justification for prescriptions. Of note, unbranded adalimumab biosimilars are included in CVS Caremark and Express Scripts’ national preferred formulary (NPF).  In the midst of the coverage shuffle, Humira’s market position has begun to weaken as biosimilar adalimumab products make further inroads.  Nevertheless, Humira still occupies roughly three quarters of the market in the US. Among the approved adalimumab biosimilars, Hyrimoz has gained substantial traction, accounting for around 15-20% of the adalimumab market, facilitated by its partnership with Cordavis, a CVS subsidiary that pushed for its inclusion in the Caremark preferred formulary.
  阿达木单抗生物类似药自上市以来，其市场格局已发生快速变化。这些生物类似药的核心差异在于能否纳入药房福利管理公司（PBM）的处方集。上市速度、浓度规格、可互换性状态、定价策略等因素似乎影响较小。2024 年 4 月，美国最大 PBM 之一 CVS Caremark 率先将修美乐移出全国优选处方集，转而纳入阿达木单抗生物类似药版本。紧随这一趋势，2025 年 OptumRx 成为唯一保留修美乐的主要 PBM，但将其降至三级用药，需额外提供处方合理性证明。值得注意的是，CVS Caremark 和 Express Scripts 的全国优选处方集（NPF）已纳入无品牌标识的阿达木单抗生物类似药。在医保覆盖变局中，随着生物类似药持续渗透，修美乐的市场地位开始松动。不过在美国市场，修美乐仍占据约四分之三的份额。 在已获批的阿达木单抗生物类似药中，Hyrimoz 通过与 CVS 子公司 Cordavis 的合作获得了显著的市场份额，约占阿达木单抗市场的 15%-20%，Cordavis 推动其纳入 Caremark 优先处方集起到了关键作用。

Speed to market  快速上市

• In early 2023, Amgen's Amjevita was the first biosimilar launched in the US as it was already a top-selling adalimumab option in Europe. Within the same year, Hyrimoz, Cyltezo, Hadlima, Hulio, Yusimry, Yuflyma, Idacio, and Abrilada entered the US market.
  2023 年初，安进的 Amjevita 成为美国首个上市的生物类似药，该产品在欧洲已是阿达木单抗的畅销选择。同年，Hyrimoz、Cyltezo、Hadlima、Hulio、Yusimry、Yuflyma、Idacio 和 Abrilada 相继进入美国市场。

• Alvotech’s Simlandi was the last biosimilar adalimumab to enter the US market in February 2024 after the resolution of manufacturing issues inspected by the FDA. Its high-concentration formula with interchangeability gives Simlandi a competitive edge among its peers. Following Alvotech’s partnership with Teva, Simlandi has been included in Express Scripts’ preferred formulary in 2025.
  Alvotech 公司的 Simlandi 于 2024 年 2 月作为最后一个阿达木单抗生物类似药进入美国市场，此前其生产问题已通过食品药品监督管理局的检查并得到解决。凭借可互换使用的高浓度配方，Simlandi 在同类产品中具有竞争优势。随着 Alvotech 与 Teva 达成合作，Simlandi 已被纳入 Express Scripts 公司 2025 年优先处方集。

Interchangeability and concentration
互换性与集中度

• While the extent of the value of an interchangeability designation for adalimumab biosimilars remains to be seen, Cyltezo was the first biosimilar approved as interchangeable with Humira. The designation allows branded Humira to be replaced by an interchangeable biosimilar at the pharmacy level without prior approval from the prescribing physician, subject to state laws. In addition to Cyltezo, six more biosimilars have been granted interchangeability designation, including Amjevita, Hyrimoz (only prefilled syringes), Hadlima, Abrilada, Simlandi and Yuflyma.
  虽然阿达木单抗生物类似药的可互换性认定价值仍有待观察，但 Cyltezo 是首个被批准与 Humira 可互换的生物类似药。该认定允许在药房层面用可互换生物类似药替代原研 Humira，无需处方内科医生事先批准（需遵守州法律）。除 Cyltezo 外，另有六种生物类似药获得可互换性认定，包括 Amjevita、Hyrimoz（仅预充式注射器）、Hadlima、Abrilada、Simlandi 和 Yuflyma。

• The high-strength formula (80mg/0.8mL) makes up the majority of the Humira market, given the reduced injection volume. However, many approved biosimilars are provided solely at lower concentrations, half the strength or less. Amjevita, Cyltezo, Hadlima, and Hyrimoz are available in both concentrations but Simlandi and Yuflyma are approved only at the higher strength. Hulio, Yusimry, Idacio and Abrilada only offer the low-concentration version, although a high-concentration version of Yusimry is planned. 
  高浓度配方（80 毫克/0.8 毫升）因注射量减少而占据修美乐市场的主要份额。然而，许多获批的生物类似药仅提供较低浓度版本，药效强度减半或更低。安健宁、赛妥珠单抗、海利姆和喜达诺均提供两种浓度规格，而欣普尼和优弗乐仅获批高浓度剂型。优立欧、尤赛瑞、艾达西和阿布昔拉则仅提供低浓度版本，不过尤赛瑞的高浓度剂型已在规划中。

Pricing and market access strategies
定价与市场准入策略

• Among the approved biosimilars, four (Amjevita, Hyrimoz, Yuflyma and Abrilada) are listed at a dual price and four (Cyltezo, Hulio, Idacia and Simlandi) are attached with low discount price while the other two (Hadlima and Yusimry) tagged at a high discount. Drugs with a single-digit discount price allows room for rebates, which would appeal to PBMs, while drugs with a large discount (80% or lower than Humira’s list price) can still compete in the market for uninsured, underinsured, or cost-sensitive patients who are likely to hit their deductible.
  在获批的生物类似药中，四款（Amjevita、Hyrimoz、Yuflyma 和 Abrilada）采用双重定价策略，四款（Cyltezo、Hulio、Idacia 和 Simlandi）标注为低折扣价格，另有两款（Hadlima 和 Yusimry）标记为高折扣。个位数折扣价格的药品留有返利空间，这对药品福利管理公司具有吸引力；而大幅折扣（低于修美乐定价 80%或更多）的药品仍可在面向自费患者、医保不足者或费用敏感型患者的市场中保持竞争力——这类患者往往需要自行承担免赔额。

• The adalimuamb market has changed rapidly and dramatically in the US in the initial years of biosimilar competition. In 2024, national formularies added several branded adalimumab biosimilars and began to exclude Humira. In 2025, payer interest has shifted from branded biosimilars to unbranded products, which are included in the formularies of the top two PBMs covering over half of the prescriptions in the US. Only a handful of branded biosimilars (Amjevita, Hyrimoz, Cyltezo and Simlandi) are included in the latest formularies from the top three PBMs in 2025. The largest PBM, CVS Caremark, covers three adalimumab biosimilars (Hyrimoz, Hadlima and Sandoz’ unbranded biosimilar), although these come with restrictions such as prior authorization, quantity limits, and a specialty drug tag indicating that they are subject to higher criteria and more clinical review. While Express Scripts prefers Cyltezo, Simlandi and unbranded biosimilars provided by Sandoz, Boheringer and Qallent, OptumRx only includes Amjevita in Tier 2 and Humira is moved to Tier 3. Half of the branded biosimilars (Hulio, Yusimry, Yuflyma, Idacio, Abrilada) are not listed in these major formularies and may struggle to find ground in this ever-evolving market.
  在美国生物类似药竞争初期，阿达木单抗市场发生了快速而剧烈的变化。2024 年，国家处方集新增了多个品牌阿达木单抗生物类似药，并开始将修美乐排除在外。到 2025 年，支付方关注点已从品牌生物类似药转向非品牌产品——这些产品被纳入覆盖全美半数以上处方的两大药房福利管理公司处方集。2025 年三大顶级药房福利管理公司最新处方集中，仅收录少数品牌生物类似药（安健宁、海正珠单抗、赛妥珠单抗和欣普尼）。最大药房福利管理公司 CVS Caremark 覆盖三种阿达木单抗生物类似药（海正珠单抗、哈德拉玛及山德士非品牌生物类似药），但设有事先授权、数量限制及需满足更高临床审查标准的专科药物标签等限制。Express Scripts 优先选用赛妥珠单抗、欣普尼及山德士/勃林格殷格翰/Qallent 提供的非品牌生物类似药，而 OptumRx 仅在二级目录中收录安健宁，并将修美乐降至三级目录。 半数品牌生物类似药（Hulio、Yusimry、Yuflyma、Idacio、Abrilada）未被纳入这些主要药品目录，在这个不断变化的市场中可能难以立足。

• Coherus made headlines with its partnership with the Mark Cuban Cost Plus Drug Company, offering Yusimry at steep discount of over 90% to SmithRx and RxPreferred members. However, without a high-price option to lend decent rebates to traditional PBMs that control most of the market, this retail strategy is not expected to gain significant market share. It is unlikely that insured patients would pay hundreds of dollars out of pocket for Yusimry when an alternative version of adalimumab would be covered. Consequently, in 2024, Coherus has opted to divest Yusimry to Meitheal Pharmaceuticals, a subsidiary of Hong Kong King-Friend Industrial Co., for an upfront cash payment of $40 million. This move marks Coherus as the first adalimumab biosimilar manufacturer to withdraw from this highly competitive sector.
  Coherus 与马克·库班成本加成制药公司达成合作，向 SmithRx 和 RxPreferred 会员提供折扣幅度超 90%的优西莫利（Yusimry），这一举措曾引发广泛关注。然而由于缺乏高价选项来为掌控大部分市场的传统药品福利管理公司提供可观返利，这种零售策略预计难以获得显著市场份额。当其他阿达木单抗仿制药可纳入医保时，投保患者不太可能自费数百美元购买优西莫利。因此 2024 年，Coherus 选择将优西莫利以 4000 万美元首付款出售给香港金卫工业有限公司旗下子公司美泰医药，此举使其成为首个退出这一高度竞争领域的阿达木单抗生物类似药生产商。

“I believe that biosimilars work exactly the same as originator molecules, they are cheaper, they’re no different in their administration. So, as far as my practice goes, whenever there is a biosimilar available, if it’s significantly cheaper and I can treat more patients with the biosimilar, I will certainly switch to a biosimilar.” – UK gastroenterology key opinion leader
"我认为生物类似药与原研分子完全等效，价格更便宜，给药方式也毫无差异。因此在我的临床实践中，只要存在可用的生物类似药，若其价格显著降低且能让我治疗更多患者，我一定会改用生物类似药。"——英国胃肠病学领域关键意见领袖

“I think they will help to bring the price down because it is competition.” – US gastroenterology key opinion leader
“我认为他们会帮助降低价格，因为这是竞争。”——美国胃肠病学领域关键意见领袖

US landscape of Humira biosimilars
美国 Humira 生物类似药市场格局

Anti-integrin therapies  抗整合素疗法

• Entyvio (vedolizumab) is differentiated as the only anti-integrin therapy and has secured its place as among the most clinically attractive therapy in UC. The drug has demonstrated superiority to Humira in TNF-naïve patients in the VARSITY trial, and is the preferred biologic over Humira and Remicade by physicians. A systematic review conducted by Attauabi et al. (2022) found that among biological therapy-naïve patients treated with Entyvio, 40% and 63.9% achieved clinical remission at week 14 and week 52, respectively. Another meta-analysis conducted by Solitano et al. (2023) found that vedolizumab was able to confer net benefit over anti-TNFs in patients with UC.
  安吉优（维多珠单抗）作为唯一的抗整合素疗法脱颖而出，并已在溃疡性结肠炎治疗领域确立了最具临床吸引力的疗法地位。该药物在 VARSITY 试验中对未接受过 TNF 治疗的患者显示出优于修美乐的疗效，并被医生列为优先于修美乐和类克的首选生物制剂。Attauabi 等人（2022 年）进行的系统评价发现，在使用安吉优治疗的生物制剂初治患者中，分别有 40%和 63.9%在第 14 周和第 52 周达到临床缓解。Solitano 等人（2023 年）开展的另项荟萃分析表明，维多珠单抗能为溃疡性结肠炎患者带来优于抗 TNF 药物的净获益。

• With formularies shifting to allow treatment with Entyvio on parity with anti-TNFs, a trend towards improved market access has been seen for Entyvio. The drug was the dominant treatment choice prior to COVID-19, but lost some momentum to Humira during the pandemic because of Entyvio’s intravenous administration route. In 2023, Takeda has gained an approval for subcutaneous Entyvio (Entyvio SC), imposing a tougher path for other subcutaneously administered drugs, such as Skyrizi, Tremfya, and Omvoh, to gain a foothold in the market, especially in first-line therapy. Entyvio SC, dosed every two weeks, provides a more convenient route for patients than the intravenous product. However, Entyvio SC contains citrate, which may cause injection site pain and could potentially lower patient compliance. Although Entyvio will lose exclusivity in 2026, Takeda is confident that no biosimilar launch will occur until the early 2030s because of the lifecycle management strategy including the newly approved subcutaneous (SC) formulation as well as the planned launch of a needle-free device and expansion into other indications such as active chronic pouchitis. Takeda has also initiated a Phase III trial in pediatric patients in both UC and CD.
  随着医保目录调整使 Entyvio 与抗 TNF 药物获得同等治疗地位，该药物的市场准入呈现改善趋势。在新冠疫情前，Entyvio 曾是主导性治疗选择，但由于其静脉注射给药方式，疫情期间部分市场份额被修美乐抢占。2023 年，武田制药皮下注射剂型 Entyvio（Entyvio SC）获批上市，这为其他皮下注射药物（如 Skyrizi、Tremfya 和 Omvoh）抢占市场设置了更高壁垒，尤其在一线治疗领域。相较于静脉注射剂型，每两周给药一次的 Entyvio SC 为患者提供了更便捷的用药选择。但该剂型含柠檬酸盐成分，可能导致注射部位疼痛并影响患者治疗依从性。尽管 Entyvio 将于 2026 年失去市场独占权，但武田制药相信通过生命周期管理策略（包括新获批的皮下注射剂型、计划推出的无针头注射装置以及拓展至慢性储袋炎活动期等新适应症），生物类似药在 2030 年代初之前都不会上市。 武田制药已针对儿童溃疡性结肠炎(UC)和克罗恩病(CD)患者启动 III 期临床试验

“In UC, very often vedolizumab right now is the first line, because it's safe, it works very well, and it has very good long-term efficacy. So, very often we are using vedolizumab as a first line. And you know, there was one head-to-head study showing that vedolizumab was superior to adalimumab.”- US key opinion leader
在溃疡性结肠炎治疗中，目前维多珠单抗通常作为一线用药，因为它安全性高、疗效显著且具有出色的长期有效性。因此我们经常将维多珠单抗作为首选方案。要知道，曾有头对头研究显示维多珠单抗优于阿达木单抗。——美国关键意见领袖

“For ulcerative colitis, I tend to use a lot of vedolizumab as first-line therapy if I can get it approved. I think vedolizumab is a very good ulcerative colitis drug, especially when it’s used earlier in the treatment algorithm. So, I have to say that I favor vedolizumab in that situation.” – US key opinion leader
对于溃疡性结肠炎，只要获批使用，我倾向于将维多珠单抗作为一线治疗药物。我认为维多珠单抗是治疗溃疡性结肠炎的优秀药物，尤其是在治疗算法中早期使用时。因此必须承认，在这种情况下我更青睐维多珠单抗。——美国关键意见领袖

“Vedolizumab for ulcerative colitis has several advantages. It's well tolerated. It does not come with the risk of opportunistic infections, at least not to the same extent, it is at least gut-focused, not gut-excusive as the company always pretends it to be.”- EU key opinion leader
维多珠单抗治疗溃疡性结肠炎具有多项优势。其耐受性良好，不会带来机会性感染风险（至少程度不同），且至少以肠道为靶向，而非如药企一贯宣称的那般仅作用于肠道。——欧盟关键意见领袖

“A lot of what I am seeing are people who have already been on a TNF and failed. So we would choose Entyvio or Stelara. We can actually get Entyvio a fair amount of the time first line, and we’re starting to be able to get Stelara a little bit first line as well, despite the fact that we have the biosimilar options available.” – US key opinion leader
"我接诊的多数患者已尝试过 TNF 抑制剂但治疗失败。因此我们会选择恩替西妥或乌司奴单抗。实际上我们已能在相当比例的一线治疗中使用恩替西妥，也开始能在一线少量使用乌司奴单抗——尽管现有生物类似药可选。"——美国关键意见领袖

Anti-interleukin therapies
抗白细胞介素疗法

• Stelara (ustekinumab) possesses a distinct mechanism of action and is supported by strong efficacy data. A meta-analysis by Singh et al. (2020) found that Stelara (as well as Xeljanz) was the highest-ranking drug for the induction of clinical remission in patients with prior exposure to anti-TNF inhibitors, and was found to be superior to Entyvio and Humira (not including maintenance of remission). On the other hand, Stelara’s commercial opportunity is stunted by its late market entry, as it was approved in October 2019 and lost exclusivity in September 2023. As the drug is expensive, anti-TNF inhibitors are often prioritized in formularies over Stelara. Stelara’s patent expired in the US and EU in 2023 and 2024, respectively, with a 2021 expiration date in most other countries having now passed. With multiple ustekinumab biosimilars launched in the EU and in the US in 2025, Johnson & Johnson has shifted its focus to its newer IL-23p19 inhibitor, Tremfya.
  乌司奴单抗（Stelara）具有独特的作用机制，并得到强效数据的支持。Singh 等人（2020 年）的 Meta 分析发现，在既往接受过抗 TNF 抑制剂治疗的患者中，Stelara（以及 Xeljanz）是诱导临床缓解效果最佳的药物，其疗效优于 Entyvio 和 Humira（不包括维持缓解阶段）。另一方面，Stelara 的商业机遇因其较晚上市而受限——该药物于 2019 年 10 月获批，2023 年 9 月失去市场独占权。由于定价高昂，医保目录通常优先纳入抗 TNF 抑制剂而非 Stelara。该药物在美国和欧盟的专利分别于 2023 年和 2024 年到期，其他多数国家的 2021 年专利到期时限现已届满。随着多款乌司奴单抗生物类似药将于 2025 年在欧美上市，强生公司已将重心转向其新型 IL-23p19 抑制剂 Tremfya。

• Following the launch of biosimilars in the US, Stelara sales slumped to $981m in the US in Q1 2025, a 42% drop compared to Q4 2024 which saw Stelara generate $1,699m.
  随着生物类似药在美国上市，Stelara 在 2025 年第一季度的美国销售额骤降至 9.81 亿美元，较 2024 年第四季度的 16.99 亿美元暴跌 42%。

“I think that the Stelara works a little bit faster than Entyvio.” – US key opinion leader 
"我认为 Stelara 起效速度略快于 Entyvio。"——美国关键意见领袖

Biosimilars to Stelara  Stelara 生物类似药

• In contrast to adalimumab biosimilars Cyltezo and Abrilada, the FDA's decision on Wezlana's interchangeability designation did not rely on switching studies, although Amgen conducted such a study alternating Stelara and Wezlana in psoriasis patients. This deviated from the 2019 interchangeability guidance, which required switching study data. The FDA waived the need for a switching study for Wezlana because the drug demonstrated similar safety and effectiveness profiles to Stelara through comprehensive analyses, including chemical and biological tests, comparative pharmacokinetics, efficacy, safety, and immunogenicity data in humans. Wezlana is not the first biosimilar to be granted interchangeability without a switching study. Other examples, such as Lantus biosimilars (Semglee and Rezvoglar) and Lucentis copycats (Cimerli and Byooviz), received this designation based on sufficient justification and robust scientific evidence. While Wezlana's case may not directly apply to other ustekinumab biosimilars, this regulatory trend is expected to stimulate and expedite the approval of more biosimilars across various drug classes and diseases. The FDA's planned revision of its interchangeability guidance further supports this prospect.
  与阿达木单抗生物类似药 Cyltezo 和 Abrilada 不同，食品药品监督管理局对 Wezlana 可互换性认定的决定并未依赖转换研究，尽管安进公司曾在银屑病患者中进行过 Stelara 与 Wezlana 交替使用的相关研究。这一做法偏离了 2019 年可互换性指南要求提供转换研究数据的规定。食品药品监督管理局豁免了 Wezlana 的转换研究要求，因为该药物通过化学与生物学测试、比较药代动力学、疗效、安全性及人体免疫原性数据等综合分析，已证明其安全性和有效性与 Stelara 高度相似。Wezlana 并非首个未经转换研究即获可互换性认定的生物类似药。其他案例包括 Lantus 生物类似药（Semglee 和 Rezvoglar）及 Lucentis 仿制药（Cimerli 和 Byooviz），它们均基于充分论证和坚实科学依据获得该认定。虽然 Wezlana 的案例可能无法直接适用于其他乌司奴单抗生物类似药，但这一监管趋势有望推动并加速更多跨药物类别及疾病领域的生物类似药获批。 食品药品监督管理局计划修订其可互换性指南，进一步支持了这一前景。

• Following the resolution of the CRL issued in 2023, Alvotech and Teva’s Selarsdi (Uzpruvo or AVT04) gained FDA’s approval in April 2024 and the drug was launched on 21 February 2025 becoming the second ustekinumab biosimilar on the US market. Selarsdi was also the second ustekinumab biosimilar which gained interchangeability status as Wezlana’s interchangeability exclusivity period ended on 30 April 2025. Additionally, Selarsdi has achieved regulatory success in other continents, including approval from the Japanese regulatory authority in September 2023 and, in collaboration with Stada, approval in the EU in January 2024.
  随着 2023 年发布的完全回应函问题得到解决，Alvotech 与 Teva 公司的 Selarsdi（商品名 Uzpruvo 或 AVT04）于 2024 年 4 月获得食品药品监督管理局批准，并于 2025 年 2 月 21 日上市，成为美国市场上第二款乌司奴单抗生物类似药。随着 Wezlana 的可互换性独占期于 2025 年 4 月 30 日结束，Selarsdi 也成为第二款获得可互换性地位的乌司奴单抗生物类似药。此外，该药物在其他大洲也取得了监管成功，包括 2023 年 9 月获得日本监管机构批准，以及与 Stada 合作于 2024 年 1 月获得欧盟批准。

• Sandoz has finalized a deal with Samsung Bioepis for the commercial rights to the ustekinumab biosimilar Pyzchiva (SB17) in the US and other regions, following their collaboration on Hadlima. Pyzchiva received marketing authorization from the European Commission (EC) in April 2024 and FDA approval in July 2024. Having launched in 22 markets in the EU, Pyzchiva has captured a dominant 43% of the EU market for Stelara biosimilars. Sandoz revealed that it had secured a partnership with an undisclosed PBM for a private-label version, similar to the firm’s Cordavis Hyrimoz (biosimilar adalimumab). Following the launch of Pyzchiva this year, Johnson & Johnson were quick to file a lawsuit against Samsung Bioepis citing violation of the terms of the original settlement from 2023. However, the U.S. District Court of New Jersey rejected Johnson & Johnson's request for an injunction against Samsung Bioepis on 30 April 2025 and this decision has allowed Samsung Bioepis to launch Pyzchiva in the U.S. market sublicensed to an undisclosed third-party private label.
  山德士与三星 Bioepis 就乌司奴单抗生物类似药 Pyzchiva（SB17）在美国及其他地区的商业权益达成最终协议，此前双方已就 Hadlima 展开合作。Pyzchiva 于 2024 年 4 月获得欧盟委员会（EC）的上市许可，并于 2024 年 7 月获美国食品药品监督管理局批准。该产品已在欧盟 22 个市场上市，占据 Stelara 生物类似药 43%的欧盟市场份额。山德士透露已与一家未公开的药房福利管理公司达成合作，将推出贴牌版本，类似该公司 Cordavis 品牌的 Hyrimoz（阿达木单抗生物类似药）。今年 Pyzchiva 上市后，强生迅速起诉三星 Bioepis 违反 2023 年原始和解协议条款。但 2025 年 4 月 30 日美国新泽西地区法院驳回了强生对三星 Bioepis 的禁令请求，这一裁决使得三星 Bioepis 得以通过授权给未公开第三方贴牌的方式在美国市场推出 Pyzchiva。

• Several strategic collaborations have taken place to commercialize ustekinumab biosimilars. Intas Pharmaceuticals (India) has joined the alliance of Dong-A Socio Holdings (South Korea) and Meiji Seika Pharma (Japan) that has co-developed Imuldosa (Absimky or DMB-3115). In October 2024, in addition to receiving the FDA approval, Imuldosa also received a positive opinion by Committee for Medicinal Products for Human Use (CHMP) under two brand names Imuldosa and Absimky for the European market with identical labels except for the former one omitting ulcerative colitis in its list of indications. Both received approval in the EU in December 2024. Formycon and Fresenius Kabi have reached an agreement with Johnson & Johnson to launch Otulfi (Fymskina or FYB202), which was approved in the US and EU in September 2024. Although they partnered for commercialization, they submitted separate marketing authorization applications in the EU, both receiving positive opinions from the CHMP in July 2024. In the European market, Formycon's Fymskina covers all indications approved for Stelara, while Fresenius Kabi's Otulfi does not include ulcerative colitis. Both Otulfi and Fymskina have now launched in the respective markets.
  为推进乌司奴单抗生物类似药的商业化，多家企业已达成战略合作。印度 Intas 制药加入了由韩国东亚制药控股与日本明治制果药业共同开发 Imuldosa（商品名 Absimky 或 DMB-3115）的联盟。2024 年 10 月，该药物不仅获得美国食品药品监督管理局批准，还获得欧洲人用药品委员会（CHMP）对两种品牌名称（Imuldosa 和 Absimky）的积极评价——两者在欧洲市场的标签内容完全一致，仅 Imuldosa 的适应症清单中未包含溃疡性结肠炎。二者均于 2024 年 12 月获得欧盟批准。Formycon 公司与费森尤斯卡比已与强生公司达成协议，共同推出 Otulfi（商品名 Fymskina 或 FYB202），该药物于 2024 年 9 月获美欧两地批准。尽管双方合作推进商业化，但在欧盟提交了各自的市场授权申请，并于 2024 年 7 月均获得 CHMP 积极评价。在欧洲市场，Formycon 的 Fymskina 覆盖了 Stelara 所有获批适应症，而费森尤斯卡比的 Otulfi 未包含溃疡性结肠炎。 奥图尔菲和菲姆斯金娜现已分别在各自市场推出。

• As the biosimilar landscape continues to evolve, several key players are making significant strides in the development and approval of ustekinumab biosimilars. Celltrion’s Steqeyma (CT-P43) received FDA approval and has launched in March 2025. Additionally, Steqeyma has received marketing authorization from the EC in September 2024, becoming the fourth ustekinumab biosimilar in the EU. Biocon’s Yesintek (Bmab1200) received approvals from the FDA in November 2024 and EC in February, 2025. Following a settlement and license agreement with Janssen, the drug has launched in the US in February 2025. In May 2025, Bio-Thera, a company based in China, announced that its proposed interchangeable biosimilar to Stelara, Starjemza (BAT2206), has been approved by the FDA, making it the eight ustekinumab biosimilar in the US. Bio-Thera has also filed with several other regulatory agencies, including the EMA and the China National Medical Products Administration (NMPA). Bio-Thera has partnered with Hikma where the former will be responsible for the development and manufacturing of the product, while Hikma will be responsible for commercialization in the US. China's Jiangsu Qyuns Therapeutics formed a collaboration agreement with Huadong Medicine to commercialize its copycat of Stelara, QX001S, in China and launched the product on February 12, 2025. 
  随着生物类似药领域持续发展，多家主要企业在乌司奴单抗生物类似药的研发与获批方面取得重大进展。Celltrion 公司的 Steqeyma（CT-P43）于 2025 年 3 月获得美国食品药品监督管理局批准并上市。此外，该产品已于 2024 年 9 月获得欧盟委员会上市许可，成为欧盟地区第四款乌司奴单抗生物类似药。Biocon 公司的 Yesintek（Bmab1200）先后于 2024 年 11 月获美国食品药品监督管理局批准、2025 年 2 月获欧盟委员会批准。在与强生达成和解及许可协议后，该药物于 2025 年 2 月在美国上市。2025 年 5 月，中国本土企业百奥泰宣布其 Stelara 可互换生物类似药 Starjemza（BAT2206）获美国食品药品监督管理局批准，成为美国市场第八款乌司奴单抗生物类似药。百奥泰还向欧洲药品管理局和中国国家药品监督管理局等多家监管机构提交了申请。该公司已与 Hikma 达成合作，由百奥泰负责产品研发与生产，Hikma 则负责美国市场的商业化运营。 中国江苏齐云药业与华东医药达成合作协议，在中国商业化其乌司奴单抗生物类似药 QX001S，并于 2025 年 2 月 12 日上市该产品。

• Unlike Humira which was not chosen for price negotiations under the Inflation Reduction Act (IRA), Stelara and its biosimilars will be affected by the IRA with the brand’s negotiated price taking effect from 2026. The IRA states that while a price control is in effect for the brand, the brand will be guaranteed formulary coverage (even if a biosimilar or generic is on the market with a lower cost). There is an exception to this ruling stated under CMS’ draft CY2025 Part D Redesign Program Instructions which state that if a newly available, therapeutically equivalent generic drug is added to the formulary at the same time as a brand with  maximum fair price (MFP), then the brand can be removed from the formulary or the brand’s preferred or tiered cost-sharing status can be changed. This will not affect the currently launched biosimilars as they will have to compete with Stelara for formulary positioning. However, if a biosimilar’s launch is delayed to June 2025 (typically when 2026 formularies are determined), formularies could directly substitute the new biosimilar and remove coverage for the brand entirely. This will negatively affect both Stelara and currently launched ustekinumab biosimilars.
  与未入选《通货膨胀削减法案》（IRA）价格谈判的修美乐不同，斯特拉拉及其生物类似药将受到 IRA 影响，品牌药谈判价格将于 2026 年生效。IRA 规定，当品牌药处于价格管控期间，其将获得医保目录保障（即使市场上有成本更低的生物类似药或仿制药）。但根据美国医疗保险和医疗补助服务中心（CMS）发布的 2025 年度 D 部分重新设计计划草案指引，该规定存在例外情况：若新上市的治疗等效仿制药与执行最高公平价格（MFP）的品牌药同时纳入医保目录，则该品牌药可被移出目录，或其优先分级或分层共付状态可被调整。这对已上市的生物类似药暂无影响，因为它们仍需与斯特拉拉竞争医保目录位序。但若某生物类似药延迟至 2025 年 6 月上市（通常此时将确定 2026 年医保目录），医保目录可能直接替换新生物类似药并完全取消对品牌药的覆盖。 这将不利于 Stelara 和目前已上市的乌司奴单抗生物类似药。

• With Stelara prices to be cut down 66% from 2026 subject to MFP due to the IRA, biosimilar companies are offering huge discounts to Stelara. Amgen is opting for a dual discount strategy for Wezlana compared to Stelara. Biocon’s Yesintek will have a wholesale acquisition cost of $3000, reflecting a 90% discount to Stelara, making it the lowest-priced ustekinumab biosimilar launched till date. In light of the aggressive pricing strategies from competitors, Formycon lowered its Stelara biosimilar Otulfi’s asset value by a third from $370m to $100m.
  由于《通胀削减法案》规定自 2026 年起 Stelara 价格将因 MFP 政策下调 66%，生物类似药企业正对 Stelara 实施大幅折扣。安进公司对其产品 Wezlana 采取双重折扣策略对标 Stelara。Biocon 公司的 Yesintek 批发采购价定为 3000 美元，相当于较 Stelara 降价 90%，成为迄今上市价格最低的乌司奴单抗生物类似药。面对竞争对手的激进定价策略，Formycon 将其 Stelara 生物类似药 Otulfi 的资产价值从 3.7 亿美元削减三分之至 1 亿美元。

US landscape of Stelara biosimilars
美国 Stelara 生物类似药市场格局

• Eli Lilly’s Omvoh (mirikizumab), a selective inhibitor of the p19 subunit of IL-23, gained approval in Europe and Japan in early 2023, and in the US in October 2023. With positive signals reported in the Phase II SHINE-1 study, Omvoh is being tested in the Phase III SHINE-2 study for treating pediatric patients with UC. If approved, Omvoh would become the third drug for pediatric patients following Remicade (approved by the FDA) and Simponi (under FDA review)
  礼来公司的 Omvoh（米利珠单抗）是一种 IL-23 p19 亚基的选择性抑制剂，于 2023 年初在欧洲和日本获批，并于 2023 年 10 月在美国获批。由于 II 期 SHINE-1 研究显示出积极信号，Omvoh 目前正在 III 期 SHINE-2 研究中接受测试，用于治疗儿童溃疡性结肠炎患者。若获批，Omvoh 将成为继类克（获 FDA 批准）和欣普尼（正在接受 FDA 审查）之后第三款用于儿童患者的药物。

• KOLs suggest that a more complete inhibition of IL-23 could possibly increase efficacy, and setting cross-trial comparison caveats aside, Omvoh’s selective inhibitory action appears more efficacious than that of Stelara. This is also reflected in the Phase III LUCENT 3 (Extension) trial where 81% and 82% of patients on Omvoh were able to maintain clinical remission and endoscopic improvement, respectively. Omvoh’s commercial potential will likely be stunted by the late-to-market approval and the drug will face competition from other IL-23p19-targeting agents such as Tremfya and Skyrizi during the early growth phase of its lifecycle and ustekinumab biosimilars from 2025.
  KOL（关键意见领袖）指出，更全面地抑制 IL-23 可能提升疗效。若暂不考虑跨试验比较的限制，Omvoh 的选择性抑制作用似乎比 Stelara 更有效。这一点在 III 期 LUCENT 3（延长）试验中也有所体现——使用 Omvoh 的患者分别有 81%和 82%能够维持临床缓解和内镜改善。由于获批时间较晚，Omvoh 的商业潜力可能受限，该药物在其生命周期早期增长阶段将面临 Tremfya 和 Skyrizi 等其他靶向 IL-23p19 药物的竞争，2025 年后还将面临乌司奴单抗生物类似药的冲击。

“I mean simplistically when it first comes out, mirikizumab is going to be the UC drug, and risankizumab is going to be the Crohn's. But that's more due to the approval process than the efficacy.” – US key opinion leader
"简单来说，mirikizumab 上市初期将主攻溃疡性结肠炎适应症，而 risankizumab 则会聚焦克罗恩病。但这更多是审批流程所致，而非疗效差异。"——美国关键意见领袖

• At the 2023 United European Gastroenterology conference, results for Omvoh from the LUCENT-1 trial in patients who received extended induction treatment every four weeks for three additional doses revealed that over 72.4% of patients who were deemed non-responsive in the induction phase demonstrated symptomatic remission during the 24-week extended induction period. This could incentivize physicians to extend induction in patients who are initially non-responsive, allowing a recapture of patients who would otherwise be relegated to further lines of therapy.
  在 2023 年欧洲联合胃肠病学大会上，LUCENT-1 试验针对接受延长诱导治疗（每四周追加三剂）的 Omvoh 患者数据显示：在诱导期被认为无应答的患者中，有超过 72.4%在 24 周延长诱导期内实现了症状缓解。这一结果可能促使医生对初始无应答患者延长诱导期，从而挽回那些原本需要转入后续治疗线的病例。

“I think you’re going to see a little bit better efficacy and probably a little bit better safety, and I think that will allow [mirikizumab] to continue even in the setting of generic Stelara, although I suspect a lot of insurance companies will try to steer us to towards Stelara.” – US key opinion leader
"我认为[mirikizumab]将展现出略优的疗效和可能更好的安全性，这使其即便在仿制 Stelara 上市后仍具竞争力，不过预计多数保险公司会试图引导我们转向 Stelara。"——美国关键意见领袖

“I think they will be a challenger to ustekinumab, the only trouble is that ustekinumab will come off patent in two to three years from now, I think, as ustekinumab is a multi-disease drug I assume there will be quite a few biosimilars. And what we’ve seen in the UK with biosimilars is that the price is really reduced drastically, so I think the prices for ustekinumab in two to three years’ time will be a fraction of what they are now. If it’s anything to go by what we’ve seen with TNFs, then somewhere in the range of 15–30% of what the cost is now. It will be very hard on a price basis to compete for an originator biologic, if they’re priced anything like they have been priced in the past.” – EU key opinion leader
"我认为它们将成为乌司奴单抗的有力竞争者，唯一的问题在于乌司奴单抗的专利保护期预计将在两三年后到期。鉴于乌司奴单抗是一种多疾病适应症药物，届时很可能会出现大量生物类似药。从英国市场经验来看，生物类似药上市会导致价格断崖式下跌——我预计两三年后乌司奴单抗的价格将跌至现价的零头。参照 TNF 抑制剂的历史轨迹，最终定价可能会维持在现行价格的 15%-30%区间。如果创新生物制剂仍维持既往定价策略，在价格层面将很难具备竞争力。"——欧盟领域关键意见领袖

• Another addition to the IL-23 class is AbbVie's Skyrizi (risankizumab). Skyrizi is already approved in several markets, including the US and EU in mid-2024, for Crohn’s disease, where the drug showcased its superiority over Stelara in the open-label Phase III SEQUENCE trial, and will now look to tighten its grip on the IBD market after gaining approval in the US in June 2024 followed by approval in the EU in July 2024. Skyrizi sits in the middle of the pack, cross-trial comparison caveats aside, with slightly better efficacy outcomes as compared to Omvoh but lagging behind Tremfya at the induction and maintenance stage of their respective studies, although Omvoh was able to confer better efficacy readouts in the maintenance phase of its Phase III trial. With similar efficacy and safety data across these pipeline agents, the commercial strength of the companies will play a significant role in the success of the drugs. AbbVie has a commanding commercial presence in the IBD market with Humira, and will aggressively back both Rinvoq and Skyrizi to generate revenue lost to Humira’s patent loss and subsequent biosimilar erosion. As such, Skyrizi is the most commercially attractive therapy in the drug comparator model.
  IL-23 抑制剂类别中新增的还有艾伯维的 Skyrizi（瑞莎珠单抗）。该药物已在美国和欧盟等多个市场获批用于克罗恩病治疗——在开放标签的 III 期 SEQUENCE 试验中，Skyrizi 展现了优于 Stelara 的疗效。随着 2024 年 6 月获美国批准、7 月获欧盟批准，该药将进一步巩固其在炎症性肠病（IBD）市场的地位。若忽略跨试验比较的局限性，Skyrizi 在疗效数据上处于中游水平：其诱导期和维持期疗效略优于 Omvoh，但逊色于 Tremfya（不过 Omvoh 在其 III 期试验维持阶段显示出更优的疗效结果）。鉴于这些在研药物具有相似的疗效和安全性数据，药企的商业实力将成为决定产品成败的关键因素。凭借修美乐在 IBD 市场的统治级商业布局，艾伯维将全力推动瑞福乐和 Skyrizi 的销售，以弥补修美乐专利到期及后续生物类似药冲击带来的收入损失。 因此，Skyrizi 在药物比较模型中是最具商业吸引力的疗法。

• The results from the Phase III SEQUENCE trial with Skyrizi reinforce a more selective IL-23 mechanism of action, acting on the p19 subunit of IL-23, as opposed to Stelara’s broader approach of binding to both IL-12 and IL-23. With KOLs already hinting at a better safety profile expected with a targeted approach, topline results from the trial in Crohn’s disease will also have a positive impact on Eli Lilly’s Omvoh and Johnson & Johnson’s Tremfya, which are both targeting a similar mechanism of action as Skyrizi and are expected to offset brand erosion in this class anticipated from Stelara biosimilars, which began in 2025.
  Skyrizi 在 SEQUENCE 三期临床试验中的结果强化了其更具选择性的 IL-23 作用机制——靶向 IL-23 的 p19 亚基，这与 Stelara 同时作用于 IL-12 和 IL-23 的广谱机制形成对比。由于关键意见领袖已暗示靶向治疗有望带来更好的安全性，这项针对克罗恩病的试验主要结果也将对礼来的 Omvoh 和强生的 Tremfya 产生积极影响——这两款药物与 Skyrizi 作用机制相似，预计将抵消 2025 年 Stelara 生物类似药上市后对该类药物预期的品牌侵蚀。

• Johnson & Johnson’s Tremfya (guselkumab) has shown promise in Phase IIb/III trials, and like Omvoh and Skyrizi it is also a selective inhibitor of the p19 subunit of IL-23. Johnson & Johnson reported potentially best-in-class data with a first efficacy readout for the QUASAR clinical program, where Tremfya was evaluated in adults with moderate-to-severe active UC with an inadequate response or intolerance to conventional therapies. The remission rates were comparable to Omvoh, with a 15% higher clinical remission rate compared to placebo at week 12. Data from the QUASAR maintenance study at 44 weeks bolster the excellent efficacy as seen in the induction phase with 48.9% of patients on the 200mg every four weeks dose and 45.2% of patients on the 100mg every eight weeks dose showcasing corticosteroid-free clinical remission as compared to 18.4% patients on placebo. Cross trial caveats aside, these results reinforce the best-in-class efficacy as seen in the induction phase of the trial and has earned its place as the most clinically promising drug in the drug comparator model. Johnson & Johnson has also submitted a sBLA to the FDA seeking approval of a subcutaneous induction regimen of Tremfya based on the Phase III ASTRO trial. The drug is the latest to join the UC arena, having gained approval in September 2024, making it the fourth drug of this class to join the market. Over in the EU, the European Commission (EC) approved Marketing Authorization (MA) for Tremfya for the treatment of adult patients with moderately to severely active UC who had an inadequate response, lost response, or were intolerant to either conventional therapy or biologic treatment. 
  强生公司的 Tremfya（古塞库单抗）在 IIb/III 期试验中展现出潜力，与 Omvoh 和 Skyrizi 类似，它也是 IL-23 p19 亚基的选择性抑制剂。强生公布的 QUASAR 临床项目首次疗效数据显示其可能成为同类最佳——该研究评估 Tremfya 在对传统疗法反应不足或不耐受的中重度活动性溃疡性结肠炎成人患者中的表现。其缓解率与 Omvoh 相当，第 12 周时临床缓解率较安慰剂组高出 15%。QUASAR 维持期研究 44 周数据进一步验证了诱导期的卓越疗效：每四周 200mg 剂量组 48.9%患者和每八周 100mg 剂量组 45.2%患者实现无皮质类固醇临床缓解，而安慰剂组仅为 18.4%。尽管存在跨试验差异的注意事项，这些结果巩固了该药物在试验诱导阶段展现的同类最优疗效，使其在药物对比模型中成为最具临床前景的治疗方案。 强生公司已向食品药品监督管理局提交了一份补充生物制品许可申请，寻求基于 III 期 ASTRO 试验批准 Tremfya 的皮下诱导治疗方案。该药物是溃疡性结肠炎领域的最新成员，于 2024 年 9 月获批上市，成为该类别中第四个进入市场的药物。在欧盟方面，欧洲委员会已批准 Tremfya 用于治疗对传统疗法或生物制剂治疗反应不足、失去反应或不耐受的中重度活动性溃疡性结肠炎成人患者。

• A late entry to the market, after Skyrizi and Omvoh, is bound to negatively affect sales of Tremfya. Despite this, Tremfya will have better commercial reach compared to Omvoh, as Johnson & Johnson has tremendous marketing experience in inflammatory bowel diseases. The company has three drugs in the UC market alone, with Stelara, Simponi, and Remicade. However, Stelara and Simponi lost market exclusivity in 2023 and 2024, respectively, and Johnson & Johnson will then lean on Tremfya to replace revenue lost due to biosimilar erosion. 
  作为继 Skyrizi 和 Omvoh 之后较晚进入市场的产品，Tremfya 的销售额势必会受到负面影响。尽管如此，与 Omvoh 相比，Tremfya 将拥有更好的商业前景，因为强生在炎症性肠病领域具有丰富的营销经验。仅就溃疡性结肠炎市场而言，该公司就拥有 Stelara、Simponi 和 Remicade 三款药物。然而 Stelara 和 Simponi 分别于 2023 年和 2024 年失去市场独占权，强生将依靠 Tremfya 来弥补生物类似药侵蚀导致的收入损失。

• Seeing the potential in oral formulations, Johnson & Johnson has initiated trials of its oral IL-23 inhibitor, icotrokinra. The company released positive top-line results from the Phase IIb ANTHEM-UC trial in inadequate responders. Cross-trial caveats aside, icotrokinra showcased a high placebo-adjusted clinical response rate of 36.5% compared to 33.8% with Tremfya (Phase IIb/III-QUASAR trial), 21.3% with Omvoh (Phase III - LUCENT 1 (Induction)) and 28.6% with Skyrizi (Phase IIb/III - INSPIRE). Additionally, icotrokinra was also able to demonstrate better placebo-adjusted clinical remission rates compared to other selective IL-23s in the aforementioned clinical trials, positioning itself as a strong competitor in this therapeutic class while offering a more convenient oral formulation as opposed to the approved IL-23s in the market, all of which only offer injectable formulations.  This approach from Johnson & Johnson to combine the best of both worlds sounds good in theory, and has shown encouraging early results. However, long-term outcomes and Phase III trial data are still needed to fully assess its clinical value and durability of response.
  看到口服制剂的潜力，强生公司已启动其口服 IL-23 抑制剂 icotrokinra 的临床试验。该公司公布了 IIb 期 ANTHEM-UC 试验在治疗应答不足患者中取得的积极顶线结果。尽管存在跨试验的注意事项，但 icotrokinra 展现出 36.5%的高安慰剂校正临床应答率，优于 Tremfya（IIb/III 期 QUASAR 试验的 33.8%）、Omvoh（III 期 LUCENT 1 诱导试验的 21.3%）和 Skyrizi（IIb/III 期 INSPIRE 试验的 28.6%）。此外，在上述临床试验中，icotrokinra 还展现出优于其他选择性 IL-23 抑制剂的安慰剂校正临床缓解率，使其成为该治疗类别中的有力竞争者，同时提供比市场上已获批 IL-23 抑制剂（均为注射制剂）更便利的口服剂型。强生这种兼收并蓄的策略在理论上颇具吸引力，早期结果也令人鼓舞，但仍需长期疗效数据和 III 期试验结果来全面评估其临床价值与应答持久性。

Non-biologic DMARDs  非生物制剂 DMARDs

JAK inhibitors  JAK 抑制剂

• While being efficacious in achieving clinical remission and adding the convenience of oral delivery compared to TNF inhibitors, JAK inhibitors have been plagued with safety issues, with both the FDA and EMA adding additional risk mitigation measures to reduce the risk of serious side effects such as thrombosis, cardiovascular problems and opportunistic infections. As a result, JAK therapies are limited to patients who have not responded to or cannot tolerate one or more TNF blockers for currently labeled indications, which eliminated the ability for JAK inhibitors to be used in the first-line setting. Similarly, the EMA stated that all JAK inhibitors should only be used if no suitable options are available in high-risk patients (patients aged over 65 years, those at a higher risk of major cardiovascular events, smokers or long-time ex-smokers), pushing JAK inhibitors to later lines of therapy. Nevertheless, physicians in the gastrointestinal community have opined that these adverse effects are much more pronounced in the RA population. On the other hand, the IBD patient population is younger and less prone to cardiovascular events, and this has improved physician confidence in prescribing JAK inhibitors in UC.
  尽管 JAK 抑制剂在实现临床缓解方面疗效显著，且相较于 TNF 抑制剂具有口服给药的便利性，但其安全性问题一直备受困扰。美国食品药品监督管理局和欧洲药品管理局均追加了额外的风险管控措施，以降低血栓形成、心血管问题及机会性感染等严重副作用的风险。因此，JAK 疗法目前仅限用于对一种或多种 TNF 阻滞剂无应答或不耐受的适应症患者，这导致 JAK 抑制剂无法用于一线治疗。同样，欧洲药品管理局也规定，所有 JAK 抑制剂仅应在高风险患者（65 岁以上、存在重大心血管事件高风险因素、吸烟或长期戒烟者）无其他合适治疗方案时使用，从而将 JAK 抑制剂推向了后线治疗。不过，消化病学领域的医师认为，这些不良反应在类风湿关节炎患者群体中表现得更为显著。 另一方面，IBD 患者群体更年轻且心血管事件风险更低，这增强了内科医生在溃疡性结肠炎中使用 JAK 抑制剂的信心。

• Rinvoq (upadacitinib) features as a commercially attractive therapy in our drug assessment model. The FDA has approved Rinvoq for the treatment of adults with moderately to severely active UC who have had an inadequate response or intolerance to one or more TNF blockers. Critically, AbbVie has extensive commercial resources and marketing experience with Humira, and is positioning Rinvoq as its next-generation product since Humira has already begun facing biosimilar competition in the US. Rinvoq is part of the emerging oral JAK inhibitor class, and there is only one other available drug of the same class, Xeljanz, which has been marketed in the US since 2018. Additionally, Rinvoq has the fifth highest clinical score in our model among approved therapies, considering the impressive efficacy it has demonstrated through its pivotal Phase III U-ACHIEVE and U-ACCOMPLISH trials in refractory moderate-to-severe UC patients. While it is difficult to compare across trials, the ~21–29% clinical remission (adapted Mayo Score) improvement over placebo at week eight is very competitive versus other marketed and pipeline therapies, including fellow JAK inhibitor Xeljanz (~10–13% clinical remission improvement over placebo at week eight in the OCTAVE Induction 1 and 2 trials).
  瑞福乐（乌帕替尼）在我们的药物评估模型中展现出极具商业吸引力的治疗价值。美国食品药品监督管理局已批准瑞福乐用于治疗对一种或多种 TNF 抑制剂反应不足或不耐受的中重度活动性溃疡性结肠炎成人患者。值得注意的是，艾伯维凭借修美乐积累了丰富的商业资源和营销经验，现正将瑞福乐定位为新一代产品——鉴于修美乐在美国已开始面临生物类似药竞争。作为新兴口服 JAK 抑制剂类别中的一员，目前美国市场同类药物仅有 2018 年上市的尚杰。此外，考虑到瑞福乐在关键性 III 期 U-ACHIEVE 和 U-ACCOMPLISH 试验中对难治性中重度溃疡性结肠炎患者展现的卓越疗效，该药在我们模型获批疗法临床评分中位列第五。 尽管跨试验比较存在难度，但第 8 周时临床缓解率（改良 Mayo 评分）较安慰剂提升约 21%-29%，这一数据相对于其他已上市及在研疗法（包括同为 JAK 抑制剂的 Xeljanz——在 OCTAVE Induction 1 和 2 试验中第 8 周临床缓解率较安慰剂仅提升约 10%-13%）而言极具竞争力。

"In clinical trials, Rinvoq showed its ability to rapidly control symptoms in just eight weeks for many patients and sustained responses at one year. I believe these types of improvements can make a positive difference for my patients.” – US key opinion leader
在临床试验中，瑞福乐（Rinvoq）显示出能在短短八周内为许多患者快速控制症状，并在一年内维持疗效。我相信这类改善能为我的患者带来积极影响。"——美国关键意见领袖

“I think the JAK inhibitors are ready, or virtually ready… at least a couple of those come from companies that have established portfolios in IBD, and hence it’s much easier for them to keep the momentum going in terms of creating a buzz, whereas if you’re new to the field, I think creating a buzz is a lot harder, especially if you’re a smaller company.” – EU key opinion leader
“我认为 JAK 抑制剂已经准备就绪，或者说基本就绪……至少其中几款来自在 IBD 领域已有产品组合的公司，因此它们更容易保持市场热度，而如果是该领域的新入局者，我认为造势会困难得多，尤其对小型企业而言。”——欧洲关键意见领袖

“So, the nice thing about it, at least so far, is that it seems to work in people even if they’ve been exposed to TNFs. Usually we’ll see about a 10–15% reduction in efficacy when they’ve been TNF-exposed, and we don’t see as much of a decrease with that agent. So that’s promising, and then there’s a fairly good mucosal healing rate, fairly quickly, with those medicines. So that’s also very encouraging as well… For sure [I’d like to use it more and earlier than Xeljanz]. That’s a yes with an exclamation point!” – US key opinion leader
“目前看来，它最令人欣慰之处在于即便患者曾接受过 TNF 抑制剂治疗，该药物似乎依然有效。通常这类患者会出现 10-15%的疗效下降，但这款药物未见明显疗效衰减。这很有前景，而且这些药物能相当快速地实现较好的黏膜愈合率，这同样非常令人鼓舞……毫无疑问[相比 Xeljanz 我会更早更频繁地使用它]。这是肯定的，绝对肯定！”——美国关键意见领袖

“The hunch I’ve got, from what I heard from colleagues, is that the safety data probably looks a tad better than what we’ve seen with tofacitinib. I think the idea of being slightly more selective for which JAK receptor it goes to looks a little bit better.” – EU key opinion leader
"根据我从同事那里听到的消息，我的直觉是安全性数据可能比我们在托法替尼上看到的略好一些。我认为这种对 JAK 受体选择性稍高的设计理念看起来更优。"——欧盟关键意见领袖

• Xeljanz (tofacitinib) entered the UC market as a first-in-class drug, and a meta-analysis by Singh et al. (2020) found that Xeljanz (as well as Stelara) was the highest-ranking drug for the induction of clinical remission in patients with prior exposure to anti-TNF inhibitors, and was superior to Entyvio and Humira. Another meta-analysis, conducted by Taxonera et al. (2022), confirmed the effectiveness of tofacitinib in a highly refractory population of patients with moderately to severely active UC, while showing an acceptable safety profile. On the other hand, safety issues have plagued Xeljanz, with both the FDA and EMA adding additional risk mitigation measures to reduce the risk of serious side effects seen with JAK inhibitors, and its patent is expected to expire in December 2025.
  Xeljanz（托法替尼）作为首创新药进入溃疡性结肠炎市场。Singh 等人（2020 年）的荟萃分析发现，对于曾接受抗 TNF 抑制剂治疗的患者，Xeljanz（以及 Stelara）在诱导临床缓解方面排名最高，优于 Entyvio 和 Humira。Taxonera 等人（2022 年）的另一项荟萃分析证实了托法替尼在中重度活动性溃疡性结肠炎的高难治性患者群体中的有效性，同时显示出可接受的安全性。另一方面，Xeljanz 一直受到安全性问题的困扰，美国食品药品监督管理局和欧洲药品管理局都增加了额外的风险缓解措施以降低 JAK 抑制剂可能引发的严重副作用风险，其专利预计将于 2025 年 12 月到期。

“I think the niche that Xeljanz has really taken up is for people that are refractory and have not responded to – have severe disease, who have not responded to anti-TNFs mainly because they’re wasting a lot of the drug in their stool from having really severe colitis. So it’s more of a rescue therapy than something we’re going to prescribe first line.” – US key opinion leader
"我认为 Xeljanz 真正占据的细分市场是针对那些难治性且对治疗无反应的重症患者，他们主要对抗 TNF 药物无反应是因为严重的结肠炎导致药物大量随粪便排出。因此它更像是一种挽救性治疗，而非我们会首选的处方方案。" ——美国关键意见领袖

“In our practice, third-line treatment at the moment is tofacitinib with a slight preference over ustekinumab, but that’s not a very strong preference.” – EU key opinion leader
"在我们临床实践中，目前的三线治疗选择是托法替尼，对乌司奴单抗略有偏好，但这种偏好并不十分强烈。" ——欧洲关键意见领袖

“But with tofacitinib the issues seem really that the 10mg dose had more infective side effects but also, and that was the worrying bit, it had far more thromboembolic side effects, and that was a great concern. I think we are all very aware that IBD patients have got a higher thromboembolic risk to start with and sadly, every now and then, that can end up being fatal, and hence a drug that might worsen that rather than improve that risk, we’re all quite conscious about that.” – EU key opinion leader
"但托法替尼的问题在于，10mg 剂量不仅感染性副作用更多，更令人担忧的是其血栓栓塞性副作用显著增加，这引起了极大关注。我们都知道 IBD 患者本身血栓栓塞风险就较高，不幸的是这种情况有时会致命。因此对于可能加重而非改善这种风险的药物，我们都保持高度警惕。" ——欧洲关键意见领袖

• In early September 2021, the FDA announced an increased risk of serious heart-related events such as heart attack or stroke, cancer, blood clots, and death with certain JAK inhibitors. Based on a large post-marketing safety study evaluating Xeljanz against TNF blockers in patients with rheumatoid arthritis (RA), the FDA required a more alarming warning in the label for Xeljanz, with a downstream effect on the more selective JAK1 inhibitor Rinvoq. More unexpected than the safety update, however, was that JAK therapies were limited to patients who have not responded to or cannot tolerate one or more TNF blockers for currently labeled indications, which eliminated the ability for JAK inhibitors to be used in the first-line setting.
  2021 年 9 月初，食品药品监督管理局宣布某些 JAK 抑制剂会增加严重心脏相关事件（如心脏病发作或中风）、癌症、血栓和死亡的风险。基于一项针对类风湿关节炎患者的大型上市后安全性研究（该研究将 Xeljanz 与 TNF 阻滞剂进行对比），食品药品监督管理局要求在 Xeljanz 的标签中增加更严厉的警告，这一决定对更具选择性的 JAK1 抑制剂 Rinvoq 也产生了连带影响。然而比安全更新更出人意料的是，JAK 疗法被限制用于对当前适应症中一种或多种 TNF 阻滞剂无反应或无法耐受的患者，这使得 JAK 抑制剂无法再作为一线治疗方案使用。

• In November 2022, the EMA also adopted measures to minimize the risk of serious side effects with JAK inhibitors. The recommendation stated that all JAK inhibitors should only be used if no suitable options are available in high-risk patients (patients aged over 65 years, those at a higher risk of major cardiovascular events, smokers or long-time ex-smokers), pushing JAK inhibitors to later lines of therapy. The committee also recommended JAK inhibitors to be used with caution in patients with risk factors for blood clots, and the lowest dosage to be used in patient groups at risk of venous thromboembolism. 
  2022 年 11 月，欧洲药品管理局（EMA）也采取了措施以最小化 JAK 抑制剂引发严重副作用的风险。该建议指出，对于高风险患者（65 岁以上老年人、主要心血管事件高风险人群、吸烟者或长期戒烟者），仅当无其他合适治疗方案时方可使用 JAK 抑制剂，这将 JAK 抑制剂推后至更晚的治疗线使用。委员会还建议对有血栓风险因素的患者谨慎使用 JAK 抑制剂，并对静脉血栓栓塞风险患者群体采用最低剂量。

• Jyseleca (filgotinib) scores poorly in the commercial sector of our drug assessment model, with no foreseeable launch in the US. It is, however, approved in both the EU and Japan for the treatment of adult patients with moderately to severely active UC who have had an inadequate response to conventional therapy or a biologic agent. With safety concerns preventing access and potential intense competition from other JAK inhibitors, the company has stated that it will have a "very high bar" for moving forward in IBD indications, and is unlikely to pursue the drug in the US.
  在我们的药物评估模型中，Jyseleca（非戈替尼）在商业板块表现不佳，且无在美国上市的计划。不过该药物已获欧盟和日本批准，用于治疗对传统治疗或生物制剂反应不足的中重度活动性溃疡性结肠炎成年患者。由于安全性问题限制其可及性，加之其他 JAK 抑制剂可能带来的激烈竞争，该公司表示对推进炎症性肠病适应症将设立"极高门槛"，且不太可能在美国继续开发该药物。

• In October 2023, Galapagos signed a letter of intent to transfer Jyseleca and related operations to Alfasigma of Italy. Under the agreement, Galapagos will transfer its marketing authorizations for Jyseleca in Europe and the UK, along with about 400 personnel who work on the drug's development, marketing, and commercialization. In an effort to expand within the indication, Alfasigma has announced that the company plans to initiate a Phase III trial in pediatric patients with moderate to severe UC.
  2023 年 10 月，Galapagos 签署意向书，将 Jyseleca 及相关业务转让给意大利 Alfasigma 公司。根据协议，Galapagos 将转让其在欧洲和英国对 Jyseleca 的上市许可，同时转移约 400 名从事该药物研发、营销和商业化的员工。为扩大适应症范围，Alfasigma 宣布计划在中重度溃疡性结肠炎儿科患者中启动 III 期临床试验。

   

S1P receptor modulators  S1P 受体调节剂

“So, some of them have got some minor cardiac conduction issues and minor effects on lung function. Whether these are completely non-significant things that you just pick up when you do a clinical trial program with a fine-tooth comb, I don’t think we know that yet. If they are there in real clinical practice it will really hinder their success on the market, because I think it will put people off. But it feels like these issues are all minor and maybe they don’t matter. But if there’s anything like you need to do a first dose monitoring of an oral dose in hospital for 12 hours or something like that, I think a lot of people would find that weird and it would put them off without even looking in detail why you do it. But these things might not become restrictions.” – EU key opinion leader
“所以，他们中有些人存在轻微的心脏传导问题和肺功能影响。这些是否只是你在用细齿梳进行临床试验项目时发现的完全无关紧要的现象，我认为我们目前还不清楚。如果这些问题真实存在于临床实践中，确实会阻碍它们在市场上的成功，因为我觉得这会让人望而却步。但感觉这些问题都很轻微，或许无关紧要。但如果出现类似需要住院对口服剂量进行 12 小时首剂监测之类的情况，我想很多人会觉得奇怪，甚至不去深究原因就直接放弃。不过这些可能不会成为限制条件。”——欧盟关键意见领袖

• Zeposia’s (ozanimod)clinical attractiveness score is in the middle of the pack as it produced only modest efficacy data from the Phase III TRUE NORTH trial. Although overall data were positive, clinical remission results in patients with prior TNF exposure favored the drug over placebo but were not statistically significant. Clinical response in this group of patients was also nominally statistically significant. However, Zeposia benefits from being a first-in-class therapy, compared to Velsipity coming in second. Although Zeposia is developed and marketed by marketing giant Bristol Myers Squibb, the drug has been relegated to later lines of therapy in formularies after TNF or IL-23s and require prior authorization. In December 2024, Bristol Myers Squibb announced that the company obtained marketing approval in Japan for Zeposia based on a domestic Phase II/III trial targeting Japanese patients.
  泽泊西亚（奥扎尼莫德）的临床吸引力评分处于中等水平，因为其 III 期 TRUE NORTH 试验仅显示出中等疗效数据。虽然总体数据呈阳性，但在曾接受过 TNF 治疗的患者中，该药物在临床缓解率上优于安慰剂，但未达到统计学显著性。该患者群体的临床应答率在名义上具有统计学意义。不过，作为首创新药，泽泊西亚相比后来者 Velsipity 仍具优势。尽管该药由营销巨头百时美施贵宝研发推广，但在处方指南中已被列为 TNF 或 IL-23 抑制剂之后的后续治疗方案，且需事先授权使用。2024 年 12 月，百时美施贵宝宣布基于针对日本患者的国内 II/III 期试验，泽泊西亚在日本获得上市批准。

• Pfizer’s Velsipity (etrasimod), approved in October 2023, is the latest oral agent in the UC market. The drug is a novel prospect for the market as an S1P1, S1P4, and S1P5 receptor modulator. It offers convenience as an oral therapy and has produced favorable tolerability and safety data in clinical trials, where it did not require any dose titration and exhibited minimal lowering of heart rate. However, it is not being positioned to fulfill significant unmet needs; hence it has low clinical attractiveness score. Velsipity could be further differentiated by showing effectiveness to treat inadequate responders to biologic therapies. The drug is currently approved in all major markets.
  辉瑞公司的 Velsipity（etrasimod）于 2023 年 10 月获批，是溃疡性结肠炎（UC）市场最新的口服药物。作为 S1P1、S1P4 和 S1P5 受体调节剂，该药物为市场带来了新前景。其口服给药方式便捷，在临床试验中展现出良好的耐受性和安全性——既无需剂量滴定，对心率的降低效应也微乎其微。但由于该药物并未定位解决显著未满足的临床需求，其临床吸引力评分较低。若能在生物制剂治疗应答不足的患者中证实疗效，Velsipity 或将进一步凸显差异化优势。目前该药物已在所有主要市场获得批准。

“I don’t know if there’s much to differentiate it from ozanimod, but it’s another S1P that might be an option.” – US key opinion leader
"我不确定它与 ozanimod 有多大区别，但这是 S1P 类药物的又一选择。"——美国关键意见领袖

Cytoplasmic cap-binding complex (CBC)
细胞质帽结合复合体（CBC）

• Obefazimod, a pipeline drug in Phase III studies, provides a unique mechanism in the UC treatment. The drug exerts its anti-inflammatory effects through binding to the CBC within the nucleus. On binding to the CBC, the drug reinforces the biological functions of CBC in cellular RNA biogenesis. This leads to the downregulation of translation of pro-inflammatory cytokines and chemokines like TNF-α, IL-6, CCL2/MCP-1, and IL-17, as well as Th17+ cells.
  奥贝法齐莫德作为一款处于 III 期研究阶段的在研药物，为溃疡性结肠炎治疗提供了独特机制。该药物通过与细胞核内的 CBC 结合发挥抗炎作用。在与 CBC 结合后，药物能增强 CBC 在细胞 RNA 生物合成中的生物学功能，从而下调促炎细胞因子和趋化因子（如 TNF-α、IL-6、CCL2/MCP-1 和 IL-17）以及 Th17+细胞的翻译过程。

• At week eight of the Phase IIb induction study, the drug was able to demonstrate statistically significant lowering of the Modified Mayo Score as compared to placebo. Similar results were also seen in the maintenance phase of the study, however in an open-label setting. These early results and the unique mechanism of action have garnered interest from KOLs, highlighting the unmet needs in the indication. Although these early results do impress, Phase III trial data are expected to draw a clearer picture of the drug’s efficacy and safety profile. In the Phase III trials, the drug is being tested in patients with an inadequate response to JAK inhibitors and S1P receptor modulators. With oral drugs increasingly gaining favor with physicians and patients alike, there is high hope for obefazimod among physicians. From the commercial perspective, obefazimod’s developer Abivax is relatively new in the IBD field and will have to compete with the likes of giants Pfizer, AbbVie, and Bristol Myers Squibb in the oral segment, and will therefore hope to build strategic partnerships to enhance its future prospects.
  在 IIb 期诱导研究的第八周，该药物与安慰剂相比，在改良 Mayo 评分降低方面显示出统计学显著性差异。类似的积极结果也出现在研究的维持期阶段，不过是在开放标签环境下获得的。这些早期数据及其独特的作用机制已引起关键意见领袖（KOLs）的关注，凸显了该适应症领域未被满足的医疗需求。尽管这些早期结果令人印象深刻，但 III 期试验数据有望更清晰地展现该药物的疗效和安全性特征。在 III 期试验中，该药物正在对 JAK 抑制剂和 S1P 受体调节剂应答不足的患者群体进行测试。随着口服药物日益受到医患双方的青睐，临床医生对 obefazimod 寄予厚望。从商业角度来看，obefazimod 的开发者 Abivax 在炎症性肠病（IBD）领域尚属新锐，未来必须在口服药物细分市场与辉瑞、艾伯维和百时美施贵宝等巨头竞争，因此有望通过建立战略合作伙伴关系来提升未来发展前景。

Anti-TL1A  抗 TL1A 抗体

• Another novel mechanism of action being explored in IBD is targeting the TL1A receptor. TL1A is an amplifier of pro-inflammatory cytokines and is a member of the TNF superfamily. This mechanism is implicated in the pathway of IBD, and the receptor, along with DR3, is significantly upregulated in inflamed intestinal tissues and fibrotic pathways. Although promising, KOLs have raised doubts on the mechanism of action in patients who have failed anti-TNFs, as the mechanisms target the same class of molecules.
  炎症性肠病（IBD）研究中另一个探索中的新作用机制是针对 TL1A 受体。TL1A 是促炎细胞因子的放大器，属于 TNF 超家族成员。该机制与 IBD 发病通路相关，其受体与 DR3 在发炎的肠道组织和纤维化通路中显著上调。尽管前景看好，但关键意见领袖（KOLs）对已对抗 TNF 治疗失败患者的作用机制提出质疑，因为两者靶向的是同一类分子。

• Among the molecules targeting this mechanism of action, RVT-3101 has a head start on the competition. In the Phase IIb TUSCANY-2 trial, at the expected Phase III dose in biomarker-positive and biologic-experienced individuals, the drug showed excellent clinical remission and endoscopic improvement rates, with 41% and 56% improvement over placebo, respectively. These results from the induction period show better clinical remission and endoscopic improvement rates compared to currently marketed anti-TNF antibodies such as Simponi and Humira. Eying promise in the mechanism of action, Roche entered into a multibillion-dollar agreement with Roivant where the former will have full rights to further develop and manufacture RVT-3101 and commercialize the drug in the US while commercialization in Japan will be headed by Chugai, pending clinical and regulatory success. In addition to this, Chugai also concluded a license agreement with Roche and has obtained exclusive rights for the development and marketing of the drug in Japan.
  在针对该作用机制的分子中，RVT-3101 已取得竞争优势。IIb 期 TUSCANY-2 试验显示，在生物标志物阳性且接受过生物制剂治疗的患者群体中，该药物采用预期 III 期剂量时展现出卓越的临床缓解率和内镜改善率，较安慰剂组分别高出 41%和 56%。这些诱导期数据表明，其临床缓解率和内镜改善率均优于目前已上市的抗 TNF 抗体药物（如欣普尼和修美乐）。基于该作用机制展现的潜力，罗氏与 Roivant 达成数十亿美元协议，前者将获得 RVT-3101 的全面开发权、生产权及美国市场商业化权利，而日本市场商业化将由中外制药主导（需取得临床和监管成功）。此外，中外制药还与罗氏达成许可协议，获得该药物在日本的独家开发和销售权。

• Prometheus Biosciences has also joined the race with MK-7240 (PRA023). In the Phase IIa ARTEMIS trial, which included patients who were both biologic-naïve and biologic-experienced, the drug demonstrated a 25% improvement over placebo in achieving the primary outcome of clinical remission. However, these results are not impressive. Drugs with other mechanisms of action, especially the anti-IL-23s, have demonstrated better outcomes, with Tremfya showcasing a 33.8% improvement over placebo in its Phase II trials. Phase III trials of MK-7240 have started recruiting patients, and results from the maintenance phase will be crucial in deciding the future of the mechanism of action. Merck & Co., seeing the potential in the mechanism, acquired Prometheus in 2023, and in doing so is hoping to expand its reach in the autoimmune sector.
  普罗米修斯生物科技公司也携 MK-7240（PRA023）加入了这场竞赛。在包含生物制剂初治和经治患者的 IIa 期 ARTEMIS 试验中，该药物在实现临床缓解主要终点方面较安慰剂组提升了 25%，但这一数据并不亮眼。其他作用机制的药物（尤其是抗 IL-23 制剂）已展现出更优疗效——特诺雅在 II 期试验中较安慰剂组提升 33.8%。目前 MK-7240 的 III 期试验已启动患者招募，维持期的试验结果将成为决定该作用机制前景的关键。默克公司看好该机制潜力，于 2023 年收购了普罗米修斯生物科技，以期扩大其在自身免疫领域的影响力。

Novel pipeline products are poised to diversify the UC market
创新管线产品将推动溃疡性结肠炎治疗市场走向多元化

The UC pipeline holds multiple novel prospects in terms of distinct mechanisms of action and biologics with more convenient formulations. There has been a positive response to Xeljanz as the first novel oral drug competing with biologics for UC, and other companies have recognized this opportunity to provide ease of administration, for example with oral Velsipity and Rinvoq. Companies have increasingly shifted their attention to oral medications, with some (Abivax’s obefazimod) exploring newer mechanisms, while others, such as Johnson & Johnson, hope to add an oral formulation to a currently established mechanism of action. Once these products reach the market, they will provide more options for UC patients beyond the established non-oral anti-TNF class that is currently the mainstay of treatment. It is likely that these novel products will initially compete at later lines of therapy after the anti-TNF inhibitors, given the latter’s enduring stronghold. Superior data from head-to-head trials and competitive pricing are essential to facilitate better positioning in the treatment algorithm.
UC 治疗管线在独特作用机制和更便捷剂型的生物制剂方面具有多重创新前景。作为首个与生物制剂竞争 UC 适应症的新型口服药物，Xeljanz 已获得积极反响，其他企业也意识到这种给药便利性的商业机会，例如口服制剂 Velsipity 和 Rinvoq 相继问世。药企正将注意力日益转向口服药物——部分企业（如 Abivax 的 obefazimod）探索全新机制，而强生等公司则希望在现有作用机制基础上增加口服剂型。这些产品一旦上市，将为 UC 患者提供除当前主流非口服抗 TNF 类药物之外的新选择。鉴于抗 TNF 抑制剂的持久市场优势，这些创新产品初期很可能在二线治疗领域展开竞争。要在治疗算法中获得更有利地位，头对头临床试验的优效性数据与具有竞争力的定价策略至关重要。

“Yes, there are many biotechs that are trying to develop new mechanisms of action, but so far they are very far away in terms of the development stage. Most of the companies now are reshaping from monoclonals to orals.” – EU key opinion leader
“确实，许多生物技术公司正在尝试开发新的作用机制，但从发展阶段来看，它们目前还处于非常早期的状态。现在大多数企业正从单抗类药物转向口服药物的研发。”——欧洲关键意见领袖

“I think if enough oral biologics come out that are more effective and safe, I think there is easily a chance that that could eventually happen. There is a lot of interest right now in developing so-called oral alpha-4/beta-7 integrin inhibitors or oral IL-23 inhibitors, so there are people who are working on this stuff. So, yes, it’s possible, but it’s going to take a while.” – US key opinion leader
“我认为，如果有足够多更有效且安全的口服生物制剂问世，这种情况最终很可能会发生。目前业界对开发口服α-4/β-7 整合素抑制剂或口服 IL-23 抑制剂非常感兴趣，已经有不少团队在推进相关工作。所以答案是肯定的，但这需要时间。”——美国关键意见领袖

“In my view, in the overall big picture, oral small molecules like the S1Ps and the JAKs are going to be within 4–5 years the future of therapy for IBD. I think they will largely have captured a lot of market share from the biologics. Among the orals, I think the most effective drugs we have right now are the JAK inhibitors.” – US key opinion leader
“在我看来，从宏观发展趋势来看，像 S1P 调节剂和 JAK 抑制剂这类口服小分子药物将在 4-5 年内成为 IBD 治疗的未来。它们将会从生物制剂手中夺取大量市场份额。而在口服药物中，我认为目前最有效的当属 JAK 抑制剂。”——美国关键意见领袖

“As far as oral drugs, this is a relative unmet need (currently already being filled by tofacitinib in UC). JAK inhibitors as well as the novel mechanism of action drug ozanimod are all oral and will also provide additional options for those who want to avoid intravenous/subcutaneous routes.” – US physician
“就口服药物而言，这仍是相对未满足的临床需求（目前托法替布已在溃疡性结肠炎领域填补该空白）。JAK 抑制剂以及具有新型作用机制的奥扎莫德均为口服制剂，将为希望避免静脉/皮下给药途径的患者提供更多选择。”——美国内科医生

Brands will face headwinds as the UC market is penetrated by biosimilars and generics 
随着生物类似药和仿制药进入溃疡性结肠炎市场，原研品牌将面临严峻挑战

The UC market will experience increasing attrition due to biosimilar competition. The European market has taken the brunt of biosimilar erosion, with earlier launches and more acceptance compared to other countries. In the US, biosimilars will initially face challenges in usurping branded anti-TNFs due to substantial originator rebates and exclusive contracting with payers. Over time, biosimilar penetration is anticipated to gain more momentum as international real-world evidence accumulates and long-term data support biosimilar efficacy and safety. This should allow physicians and patients to grow their confidence and familiarity with biosimilars and encourage uptake. Adalimumab biosimilars have already hit the market, and Stelara biosimilars have launched in the US in 2025, while the EU has experienced biosimilar competition from Stelara biosimilars from 2024. Furthermore, generic tofacitinib is expected to enter the US market at the end of 2025. Notably, generics have fewer barriers to entry than biosimilars due to factors including their less complex nature and longstanding familiarity, which will facilitate much faster and stronger erosion of branded sales.
由于生物类似药的竞争，UC 市场将面临日益加剧的市场份额流失。欧洲市场首当其冲受到生物类似药侵蚀的影响，相较于其他国家，其上市时间更早且接受度更高。在美国，由于原研药提供的高额返利以及与支付方签订的独家合同，生物类似药在初期抢占品牌抗 TNF 药物市场时将面临挑战。随着时间的推移，随着国际真实世界证据的积累以及长期数据对生物类似药疗效和安全性的支持，生物类似药的渗透率预计将获得更大动力。这将增强医生和患者对生物类似药的信心和熟悉度，从而促进其使用。阿达木单抗生物类似药已上市，Stelara 生物类似药于 2025 年在美国推出，而欧盟自 2024 年起便面临 Stelara 生物类似药的竞争。此外，托法替尼仿制药预计将于 2025 年底进入美国市场。值得注意的是，由于结构相对简单且长期使用形成的认知度等因素，仿制药的准入壁垒低于生物类似药，这将导致品牌药销售额以更快速度和更大幅度下滑。

“What we find in general is that a branded version and a biosimilar version of the same molecule have worked equivalently well. So whenever there’s a biosimilar of the same molecule available, we would recommend the biosimilar rather than the branded drug.” – EU key opinion leader
“我们普遍发现，同一分子的品牌药和生物类似药疗效相当。因此，只要存在相同分子的生物类似药，我们就会推荐使用生物类似药而非品牌药。”——欧盟关键意见领袖

“A lot of the time that is the issue, they want us to preferably use the biosimilar even though we feel some of the other agents might be better options for the patients. If we try to get them on an alternative agent it takes weeks to months to get it approved, because it takes a while to get someone to do a peer-to-peer review, and then half the time you lose anyway so it’s almost not worth their time, and I think that’s the whole point of that whole process actually.” – US key opinion leader
“很多时候问题在于，即便我们认为其他药物可能对患者更有利，他们仍希望我们优先使用生物类似药。如果我们尝试让患者改用其他药物，审批流程往往需要数周甚至数月——因为光是安排同行评审就要耗费很长时间，而且半数情况下申请最终会被驳回，整个过程几乎得不偿失。我认为这恰恰是该流程设计的初衷。”——美国关键意见领袖

“If you think back about the difference between the price of infliximab and vedolizumab, vedolizumab was a bit more expensive but not much. It was probably about 20% or 30% more expensive. Then biosimilars came in and the price difference rose to initially about 150% and eventually it was 300% as expensive as infliximab. And at that stage you’re really in a situation where you say, how can I justify using a far more expensive drug that I think is equivalent in terms of efficacy, and then you don’t. So if prices reduce, I think it makes it harder to justify using a more expensive drug.” – EU key opinion leader
回顾英夫利昔单抗与维多珠单抗的价格差异，维多珠单抗稍贵但差距不大，约高出 20%至 30%。随着生物类似药上市，价差最初扩大到约 150%，最终达到英夫利昔单抗价格的 3 倍。此时你会陷入困境：如何证明使用疗效相当却昂贵得多的药物是合理的？最终只能放弃。因此若价格下降，我认为更难合理化使用更昂贵的药物。——欧盟关键意见领袖

This is a snapshot of quotes from KOLs interviewed by our analysts. To view complete interviews, access KOL Insights.

“We probably have about 40% of our patients [who have failed first-line TNF therapies or have severe disease] on Entyvio. Stelara’s probably closer to about 20%, and then Remicade maybe another 25%, and then probably 10% is sort of miscellaneous other therapies. And I’m lumping in the biosimilars under Remicade… so maybe about 40% of our [infliximab] patients have been switched to Inflectra, mainly because of insurance mandates.” – US key opinion leader

“Well, unfortunately the number one thing that drives our prescribing is the insurance, which medication is preferred, because nowadays it’s almost impossible to get a medicine if it’s not the preferred option on the patient’s insurance plan, even if you don’t feel it’s the best option for the patient.” – US key opinion leader

“So in terms of the overall cohort of patients with ulcerative colitis, I would imagine that we’ve got, at the moment, about 15% on the advanced therapies, and that’s slowly increasing. When you look at those 15% and you split those up further – and I’m making the 15 now 100 again just for ease – probably about 60% are on infliximab, about 30% on vedolizumab, and then the rest is a smattering around the other agents.” – EU key opinion leader

“Now, when you’re balancing safety versus efficacy, I always think that efficacy is really important and safety is the second consideration, unless patients have got significant side effects or are at risk – you know, like elderly patients or those with lots of co-morbidities. And then a third consideration is really the practical aspects, and that includes how the drug is given and what the costs are to the health service. When you have a drug that you think is as efficacious as another one and there’s a big price difference, then we would have a preference for the cheaper one first rather than the more expensive one first.” – EU key opinion leader

More research of the etiology of UC

Beyond improving symptoms and inducing remission, disease-modifying agents are needed to prevent extended and irreversible consequences of disease activity, including bowel damage and the need for colectomy. However, this is challenging considering that the etiology of the disease is yet to be clearly identified.

“Because the etiology of ulcerative colitis has not been definitively defined, treatment involves suppressing different aspects of the inflammatory cascade. These include therapies that suppress cytokines, including interleukins, as well as cell signaling proteins such as Janus kinase. Drugs in development continue these approaches to treating the disease. They include IL-23 antagonists, new Janus kinase inhibitors, an entirely different class of drugs called S1P receptor antagonists (e.g., ozanimod, etrasimod), and others. Results from clinical trials thus far, in general, show good efficacy and reasonable safety, but they are more graduated than revolutionary improvements.” – US physician

“People that have really severe proctitis, in particular, we don’t have a lot of great options for those people, and the only thing we’re really using would be steroid suppositories, 5-ASA suppositories or enemas. So something novel would be wonderful. And people with reactive inflammation in the rectum, in particular, really have quite severe, or can have quite severe symptoms, even with the rest of the colon being healed. So that would be great.” – US key opinion leader

“[Another] unmet need has to do with the tendency of distal or left-sided colitis, or even proctitis, to undergo late spread. I mean often ulcerative colitis presents in the rectum, and then within a few months it’s spread proximally, that’s common, but the bigger problem is proctitis that has been stable for 6–12 months, two years, and then spreads proximally. That doesn’t creep up, it spreads like wildfire and it’s very severe, and an unmet need is to be able to predict which patients will have that late, severe spread, and to prevent it from happening.” – US key opinion leader

Effective, well-tolerated treatments that induce rapid and sustained remission

Treatment goals are primarily oriented towards remission; this is crucial as uncontrolled inflammation may raise the risk for dysplasia and colon cancer. Corticosteroid-free remission is another goal, as corticosteroids have burdensome side effects. Other drug classes have their own drawbacks, such as an increased risk of infection with anti-TNFs. Physicians value earlier clinical remission, with a desire for drugs that achieve clinical remission by four weeks and histologic remission by one year.

“So, I don’t see why we couldn’t move quickly to other pretty safe agents that are good at inducing as well as maintaining remission. I would think in my view right now, the JAK inhibitors are looking pretty much the best for that purpose, and I think as people come to recognize that the black box warnings really do not apply to our population of IBD patients as opposed to rheumatoid arthritis, as people come to recognize that if you’ve induced remission with, say, 10mg twice a day, you should maintain that rather than follow the advice of dropping back to 5mg twice a day, because you get so many relapses if you do that. I think once people have gotten more comfortable with their use, that they could very well become first-line agents.” – US key opinion leader

“With regards to biologic options, there needs to be more options with rapid onset of action (clinical remission as fast as four weeks) and with more histologic remission at the one-year mark (even in those who have previously tried and failed an anti-TNF).” – US physician

 

There is critical unmet need for predictive biomarkers

Physicians emphasize the need for predictive biomarkers that will facilitate the implementation of effective treatment regimens earlier. Currently, it may take months to establish a response and identify non-responders to treatment. Thus, a stratified medicine approach would have the potential to radically improve the efficiency of treatment and treatment outcomes. In clinical trials, primary and secondary non-responders to anti-TNFs may represent 19–58% and 17–22% of patients, respectively. Furthermore, approximately 68–77% of second-line patients discontinue anti-TNFs after a year due to a loss of response.

“I think one of the things that we don’t really have in IBD is we don’t have a lot of sequencing data. So something that would give us some idea of how these agents – and that applies for the new JAKs – work in people that have been exposed to TNFs or Entyvio or Stelara, just so we can get a better sense of whether it might work better before one or if it works better after. So any kind of sequencing information would be helpful, and then any sort of biomarker or any way to predict who might respond to that, to sort of inform our decision, would be very helpful too.” – US key opinion leader

“The frustration with our whole field is that we don’t have predictive molecular biomarkers, like the oncologists have, so when we’re picking drugs it’s largely empiric, and it would be nice to have precision medicine where we could say, ah, you are going to respond to this class or you’re going to respond to that class. Right now, it’s sort of a shot in the dark. So, I feel like that would be a huge advance, but how close are we to that, I don’t know.” – US key opinion leader

“This is the Holy Grail, a risk stratification tool that tells us which drug is the right drug for a patient, which drug are they most likely to respond to. Because at the moment you sequence them either by cost, by safety, by efficacy, or pretty randomly, but we don’t have a way of saying, actually patient A, having looked at all his markers, will likely respond to infliximab best, and patient B to vedolizumab, and patient C should go onto tofacitinib first line. If we had a way of approaching that a little bit more rationally and a little bit more individualized that would really be fantastic. But I think a lot of people have looked into developing the right biomarkers and so far there’s relatively little success.” – EU key opinion leader